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The American Journal of Gastroenterology Sep 2020Achalasia is an esophageal motility disorder characterized by aberrant peristalsis and insufficient relaxation of the lower esophageal sphincter. Patients most commonly...
Achalasia is an esophageal motility disorder characterized by aberrant peristalsis and insufficient relaxation of the lower esophageal sphincter. Patients most commonly present with dysphagia to solids and liquids, regurgitation, and occasional chest pain with or without weight loss. High-resolution manometry has identified 3 subtypes of achalasia distinguished by pressurization and contraction patterns. Endoscopic findings of retained saliva with puckering of the gastroesophageal junction or esophagram findings of a dilated esophagus with bird beaking are important diagnostic clues. In this American College of Gastroenterology guideline, we used the Grading of Recommendations Assessment, Development and Evaluation process to provide clinical guidance on how best to diagnose and treat patients with achalasia.
Topics: Disease Management; Esophageal Achalasia; Esophageal Sphincter, Lower; Humans; Manometry; Peristalsis
PubMed: 32773454
DOI: 10.14309/ajg.0000000000000731 -
Romanian Journal of Internal Medicine =... Mar 2021Gastroesophageal reflux disease (GERD) is considered one of the most frequent chronic gastrointestinal diseases globally with high costs due to treatment and... (Review)
Review
Gastroesophageal reflux disease (GERD) is considered one of the most frequent chronic gastrointestinal diseases globally with high costs due to treatment and investigations.First line therapy is with proton pump inhibitors, those who do not respond to initial treatment usually require further investigations such as upper gastrointestinal endoscopy or ambulatory 24-hours esophageal pH monitoring. The total time of exposure to acid and the DeMeester score represent the most useful parameters associated with conventional pH-metry, because they can identify gastroesophageal reflux disease.Although pH-metry is considered the gold standard for the evaluation of gastroesophageal reflux disease, new impedance-based parameters have been introduced in recent years with the role of increasing the accuracy of diagnosing gastroesophageal reflux disease and characterizing the type of reflux. The development of multichannel intraluminal pH-impedance has improved the ability to detect and quantify gastroesophageal reflux. New parameters such as post-reflux swallowing peristaltic wave (PSPW) index and the mean nocturnal basal impedance (MNBI) have recently been introduced to assess GERD phenotypes more accurately. This review evaluates current GERD diagnotic tools while also taking a brief look at newer diagnostic parameters like PSPW and MNBI.
Topics: Diagnostic Techniques, Digestive System; Electric Impedance; Endoscopy, Digestive System; Esophageal pH Monitoring; Gastroesophageal Reflux; Humans; Peristalsis; Proton Pump Inhibitors
PubMed: 33010143
DOI: 10.2478/rjim-2020-0027 -
Nature Feb 2020Neural control of the function of visceral organs is essential for homeostasis and health. Intestinal peristalsis is critical for digestive physiology and host defence,...
Neural control of the function of visceral organs is essential for homeostasis and health. Intestinal peristalsis is critical for digestive physiology and host defence, and is often dysregulated in gastrointestinal disorders. Luminal factors, such as diet and microbiota, regulate neurogenic programs of gut motility, but the underlying molecular mechanisms remain unclear. Here we show that the transcription factor aryl hydrocarbon receptor (AHR) functions as a biosensor in intestinal neural circuits, linking their functional output to the microbial environment of the gut lumen. Using nuclear RNA sequencing of mouse enteric neurons that represent distinct intestinal segments and microbiota states, we demonstrate that the intrinsic neural networks of the colon exhibit unique transcriptional profiles that are controlled by the combined effects of host genetic programs and microbial colonization. Microbiota-induced expression of AHR in neurons of the distal gastrointestinal tract enables these neurons to respond to the luminal environment and to induce expression of neuron-specific effector mechanisms. Neuron-specific deletion of Ahr, or constitutive overexpression of its negative feedback regulator CYP1A1, results in reduced peristaltic activity of the colon, similar to that observed in microbiota-depleted mice. Finally, expression of Ahr in the enteric neurons of mice treated with antibiotics partially restores intestinal motility. Together, our experiments identify AHR signalling in enteric neurons as a regulatory node that integrates the luminal environment with the physiological output of intestinal neural circuits to maintain gut homeostasis and health.
Topics: Animals; Basic Helix-Loop-Helix Transcription Factors; Cytochrome P-450 CYP1A1; Female; Gastrointestinal Microbiome; Germ-Free Life; Intestines; Ligands; Male; Mice; Neural Pathways; Neurons; Peristalsis; Receptors, Aryl Hydrocarbon; Signal Transduction; Transcriptome
PubMed: 32025031
DOI: 10.1038/s41586-020-1975-8 -
International Journal of Molecular... Jun 2020Millions of patients worldwide suffer from gastrointestinal (GI) motility disorders such as gastroparesis. These disorders typically include debilitating symptoms, such... (Review)
Review
Millions of patients worldwide suffer from gastrointestinal (GI) motility disorders such as gastroparesis. These disorders typically include debilitating symptoms, such as chronic nausea and vomiting. As no cures are currently available, clinical care is limited to symptom management, while the underlying causes of impaired GI motility remain unaddressed. The efficient movement of contents through the GI tract is facilitated by peristalsis. These rhythmic slow waves of GI muscle contraction are mediated by several cell types, including smooth muscle cells, enteric neurons, telocytes, and specialised gut pacemaker cells called interstitial cells of Cajal (ICC). As ICC dysfunction or loss has been implicated in several GI motility disorders, ICC represent a potentially valuable therapeutic target. Due to their availability, murine ICC have been extensively studied at the molecular level using both normal and diseased GI tissue. In contrast, relatively little is known about the biology of human ICC or their involvement in GI disease pathogenesis. Here, we demonstrate human gastric tissue as a source of primary human cells with ICC phenotype. Further characterisation of these cells will provide new insights into human GI biology, with the potential for developing novel therapies to address the fundamental causes of GI dysmotility.
Topics: Gastrointestinal Diseases; Gastrointestinal Motility; Gastrointestinal Tract; Humans; Interstitial Cells of Cajal; Intestine, Small; Myocytes, Smooth Muscle; Peristalsis; Stomach
PubMed: 32630607
DOI: 10.3390/ijms21124540 -
Immunity Jan 2021The gastrointestinal tract is known as the largest endocrine organ that encounters and integrates various immune stimulations and neuronal responses due to constant...
The gastrointestinal tract is known as the largest endocrine organ that encounters and integrates various immune stimulations and neuronal responses due to constant environmental challenges. Enterochromaffin (EC) cells, which function as chemosensors on the gut epithelium, are known to translate environmental cues into serotonin (5-HT) production, contributing to intestinal physiology. However, how immune signals participate in gut sensation and neuroendocrine response remains unclear. Interleukin-33 (IL-33) acts as an alarmin cytokine by alerting the system of potential environmental stresses. We here demonstrate that IL-33 induced instantaneous peristaltic movement and facilitated Trichuris muris expulsion. We found that IL-33 could be sensed by EC cells, inducing release of 5-HT. IL-33-mediated 5-HT release activated enteric neurons, subsequently promoting gut motility. Mechanistically, IL-33 triggered calcium influx via a non-canonical signaling pathway specifically in EC cells to induce 5-HT secretion. Our data establish an immune-neuroendocrine axis in calibrating rapid 5-HT release for intestinal homeostasis.
Topics: Animals; Calcium Signaling; Enterochromaffin Cells; Homeostasis; Interleukin-33; Intestines; Mice; Mice, Inbred C57BL; Mice, Knockout; Neuroimmunomodulation; Neurons; Peristalsis; Serotonin; Trichuriasis; Trichuris
PubMed: 33220232
DOI: 10.1016/j.immuni.2020.10.014 -
Therapeutische Umschau. Revue... Apr 2022Achalasia Update The neurodegenerative disease achalasia (obsolete: "cardiac spasm") is the second most common functional disease of the esophagus after reflux disease....
Achalasia Update The neurodegenerative disease achalasia (obsolete: "cardiac spasm") is the second most common functional disease of the esophagus after reflux disease. It is associated with an extremely high level of suffering for the patient. Pathophysiologically, it is a combination of a lack of swallowing-reflex relaxation at the gastric entrance and disturbed peristalsis of the tubular esophagus. The gold standard in diagnostics is high-resolution manometry. The disease cannot be cured, the therapeutic spectrum that alleviates the disease includes pharmaceutical, endoscopic-interventional and surgical procedures.
Topics: Esophageal Achalasia; Humans; Manometry; Neurodegenerative Diseases; Peristalsis
PubMed: 35440187
DOI: 10.1024/0040-5930/a001339