1,721,026 research outputs found
Intestinal Permeability In Non-Alcoholic Fatty Liver Disease: The Gut-Liver Axis
No full textThe gut-liver axis model has helped to explain the liver steatosis (NAFLD) and steatohepatitis (NASH) etiopathogenesis. The discovery of a key role for an altered intestinal permeability (IP) in this pathophysioligcal framework has closed the link between gut lumen antigenic/toxic substances and systemic and liver inflammation in NAFLD and obesity, metabolic syndrome. Recent evidences from the literature show how IP can be modulated by several non-pharmacological and pharmacological agents and be the target for future preventive and curative treatment of NAFLD and NASH. In this review we describe the concept of IP, its ultrastructural basis, its role in the NALFD pathophysiology and emerging evidences on non-pharmacological and pharmacological agents able to favourable modulate it
Effect of baclofen on the acid pocket at the gastroesophageal junction
No full textPrevious studies established that a pocket of highly acidic gastric juice is present postprandially at the gastroesophageal junction in man. The GABA-B agonist baclofen inhibits postprandial reflux events through its effects on the lower esophageal sphincter (LES). The aim of the current study was to investigate whether baclofen would affect the location and the extent of the postprandial acid pocket in healthy volunteers. Twelve healthy volunteers underwent acid pocket studies on two different occasions, at least 1 week apart. LES position was determined preprandially with pull-through manometry. Dual pH electrode and manometry probe stepwise pull-through (1 cm/minute, LES-10 to +5 cm) was performed at 30-minute intervals for 150 minutes, with administration of placebo or baclofen 40 mg after the first and ingestion of a liquid meal after the second pull-through. After placebo, a significant drop in intragastric gastric pH was present at the gastroesophageal junction after the meal, reflecting the acid pocket, and this was associated with a drop in LES pressure. Baclofen did not affect the presence of the acid pocket, but prevented the postprandial drop in LES pressure, and the extent of the acid pocket above the upper margin of the manometrically located LES was significantly decreased by baclofen (1.6 ± 0.7 vs. 0.3 ± 0.4 cm at 60 minutes, 2.2 ± 0.6 vs. 0.2 ± 0.6 at 90 minutes, and 1.5 ± 0.5 vs. 0.7 ± 0.7 cm at 120 minutes, all P < 0.05). Baclofen does not alter the intragastric acid pocket, but limits its extension into the distal esophagus, probably through an increase in postprandial LES pressure
The human gut microbiota and virome: Potential therapeutic implications
No full textHuman gut microbiota is a complex ecosystem with several functions integrated in the host organism (metabolic, immune, nutrients absorption, etc.). Human microbiota is composed by bacteria, yeasts, fungi and, last but not least, viruses, whose composition has not been completely described. According to previous evidence on pathogenic viruses, the human gut harbours plant-derived viruses, giant viruses and, only recently, abundant bacteriophages. New metagenomic methods have allowed to reconstitute entire viral genomes from the genetic material spread in the human gut, opening new perspectives on the understanding of the gut virome composition, the importance of gut microbiome, and potential clinical applications. This review reports the latest evidence on human gut "virome" composition and its function, possible future therapeutic applications in human health in the context of the gut microbiota, and attempts to clarify the role of the gut "virome" in the larger microbial ecosystem
The effects of itopride on oesophageal motility and lower oesophageal sphincter function in man
No full textBACKGROUND:
Itopride is a new prokinetic agent that combines antidopaminergic and cholinesterase inhibitory actions. Previous studies suggested that itopride improves heartburn in functional dyspepsia, and decreases oesophageal acid exposure in gastro-oesophageal reflux disease. It remains unclear whether this effect is due to effects of itopride on the lower oesophageal sphincter (LES).
AIMS:
To study the effects of itopride on fasting and postprandial LES function in healthy subjects.
METHODS:
Twelve healthy volunteers (five men; 32.6 ± 2.0 years) underwent three oesophageal sleeve manometry studies after 3 days premedication with itopride 50 mg, itopride 100 mg or placebo t.d.s. Drug was administered after 30 min and a standardized meal was administered after 90 min, with measurements continuing to 120 min postprandially. Throughout the study, 10 wet swallows were administered at 30-min intervals, and gastrointestinal symptoms were scored on 100 mm visual analogue scales at 15-min intervals.
RESULTS:
Lower oesophageal sphincter resting pressures, swallow-induced relaxations and the amplitude or duration of peristaltic contractions were not altered by both doses of itopride, at all time points. Itopride pre-treatment inhibited the meal-induced rise of transient LES relaxations (TLESRs).
CONCLUSIONS:
Itopride inhibits TLESRs without significantly affecting oesophageal peristaltic function or LES pressure. These observations support further studies with itopride in gastro-oesophageal reflux disease
Eluxadoline for the treatment of diarrhoea-predominant irritable bowel syndrome
No full textABSTRACT: Introduction: Irritable bowel syndrome (IBS) treatment is challenging physicians because of its multifactorial physiopathology. In particular, abdominal pain and diarrhea management lack one unique effective pharmacological remedy. Opioid receptors, present in the central nervous system (CNS) and the enteric nervous system (ENS), are involved in visceral sensitivity and gastrointestinal motility control. To date only a few opioid receptor modulators are currently in use for the treatment of IBS but with dosage limitations due to the early development of severe constipation. Areas covered: In this drug evaluation manuscript we review the irritable bowel syndrome therapeutic needs and chemistry, pharmacokinetics and -dynamics, clinical study results with the new opioid receptor ligand eluxadoline for the treatment of diarrhea-predominant irritable bowel syndrome (IBS-D). Expert opinion: Eluxadoline shows a peculiar pharmacological profile with μ-opioid agonism and δ-opioid antagonism actions. Its efficacy over placebo for the treatment of abdominal pain and diarrhea in IBS-D has been demonstrated in short- and long-term clinical studies in humans. Its safety has been evaluated in the same studies. Interestingly, eluxadoline showed a low rate of constipation development in IBS patients in comparison with known effects of other opioid receptor modulators. Patients with a history of acute pancreatitis should not be treated with eluxadoline
Probiotics in non-alcoholic fatty liver disease: which and when
No full textNon-alcoholic fatty liver disease (NAFLD) is a common and serious disease. Literature reports the central role of the gut-liver axis in the pathogenesis of NAFLD, and recently suggests that the nnicrobiota is a casual factor of the disease, involved in the interactions between intestinal lumen and liver. Probiotic are commensal bacteria, able to modulate the microbiota with benefits for the health of humans. Several data suggest a range of potentially beneficial medicinal uses for probiotics, in particular in NAFLD patients. However, the species with higher efficacy in this disease are not identified. The present review focuses on the role of gut-liver axis in the pathogenesis, and on the potential therapeutic role of probiotics in the managing of NAFLD
ag) Prevalence of small intestinal bacterial overgrowth in children with irritable bowel syndrome: a case-control study.
No full textOBJECTIVE: To assess the prevalence of small intestinal bacterial overgrowth (SIBO) in children affected by irritable bowel syndrome (IBS). STUDY DESIGN: Consecutive children affected by IBS according to Rome II criteria (n = 43) were enrolled at the Gemelli Hospital, Catholic University of Rome. The control population (n = 56) consisted of healthy subjects without IBS symptoms, similar to patients for age, sex, and social background. All subjects underwent lactulose/methane breath test (LBT) to assess small intestinal bacterial overgrowth. RESULTS: The prevalence of abnormal LBT result was significantly higher in patients with IBS (65%, 28/43) with respect to control subjects (7%, 4/56; OR 3.9, 95% CI 7.3-80.1, P < .00001). Patients with abnormal LBT showed a trend toward a worse visual analog scale score with respect to children with IBS without SIBO, but a significant statistical difference was observed only for bloating. CONCLUSIONS: Results from this study suggest a significant epidemiologic association between SIBO and IBS in childhood. Placebo-controlled interventional studies with antibiotics used to treat bacterial overgrowth are warranted to clarify the real impact of the disease on IBS symptoms
Intestinal Permeability In Non-Alcoholic Fatty Liver Disease: The Gut-Liver Axis.
No full textThe gut-liver axis model has helped to explain the liver steatosis (NAFLD) and steatohepatitis (NASH) etiopathogenesis. The discovery of a key role for an altered intestinal permeability (IP) in this pathophysioligcal framework has closed the link between gut lumen antigenic/toxic substances and systemic and liver inflammation in NAFLD and obesity, metabolic syndrome. Recent evidence from the literature show how IP can be modulated by several non-pharmacological and pharmacological agents and be the target for future preventive and curative treatment of NAFLD and NASH. In this review we describe the concept of IP, its ultrastructural basis, its role in the NALFD pathophysiology and emerging evidence on non-pharmacological and pharmacological agents able to favourably modulate it
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