Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0014848 (achalasia)
 2,804 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Australian surgeons have been prominent in the introduction, development, and consolidation of laparoscopic surgery of the upper gut. In doing this, some of the very best principles of surgical innovation have been in evidence: preliminary animal work in which to test hypotheses and techniques, followed by careful application and documentation in the clinical setting, randomized clinical trials and finally academic reporting and ongoing development. This review documents the introduction of laparoscopic surgery for gastroesophageal reflux, hiatus hernia, achalasia, gastroesophageal malignancy, obesity, and a range of emergency conditions in Australia. Those involved are regarded as world leaders in their field. A vital component of this success has been the close cooperation between surgeons and gastroenterologists within the Gastroenterological Society of Australia.
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PMID:Laparoscopic upper gut surgery. 1979 92

One year before the close of the 19th century it was recognized that intestinal peristalsis was controlled by nerve plexuses in the wall of the gut independent of the central nervous system (CNS). This concept was developed further during the first quarter of the 20th century but was almost forgotten during the next 50 years until it was revived by the early 1970s. It is now recognized that the myenteric and submucous plexuses, referred to as the enteric nervous system (ENS), contain as many neurons as in the spinal cord. In addition to autonomy from the CNS, the ENS employs not only noradrenaline and acetylcholine but also serotonin (5-HT), ATP, peptides and nitric oxide as neurotransmitters, and controls gut movements, exocrine and endocrine secretions and the microcirculation, thus qualifying for being considered the brain of the gut. Reflexes involving the ENS may be entirely intrinsic such as that controlling peristalsis, between parts of the gut through prevertebral ganglia e.g. the enterogastric reflex, or between the gut and the CNS as examplified by the vago-vagal reflexes. Absent, defective or dysfunctional enteric neurons may result in achalasia, infantile hypertrophic pyloric stenosis, paralytic ileus, intestinal pseudo-obstruction, Hirschsprung's disease or idiopathic chronic constipation. Further, the ENS may be involved in the pathogenesis of secretory diarrhoea and inflammatory bowel disease. More research on the gut brain will deepen our understanding of the physiology and pathophysiology of the gastrointestinal tract.
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PMID:The brain of the gut. 1986 24

Nitric oxide (NO) is a functionally important neurotransmitter signaling molecule generated by mammalian and bacterial nitric oxide synthases (NOS), and by chemical conversion of dietary nitrite in the gastrointestinal (GI) tract. Neuronal NOS (nNOS) is the most abundant isoenzyme in the enteric nervous system, and targeted deletion in transgenic mice has clearly demonstrated its importance in normal gut function. Enteric neuropathy is also often associated with abnormal NO production, for example in achalasia and diabetic gastroparesis. Not surprisingly therefore, aberrant nNOS activity is widely implicated in enteric disease, and represents a potential molecular target for therapeutic intervention. One physiological signaling mechanism of NO bioactivity is through chemical reaction with the heme center of guanylyl cyclase, resulting in the conversion of cGMP from GTP. This second messenger nucleotide signal activates cGMP-dependent protein kinases, phosphodiesterases, and ion channels, and is implicated in the neuronal control of GI function. However, few studies in the GI tract have fully related NO bioactivity with specific molecular targets of NO-derived signals. In the central nervous system (CNS), it is now increasingly appreciated that NO bioactivity is often actively transduced via S-nitrosothiol (SNO) signals rather than via activation of guanylyl cyclase. Moreover, aberrant S-nitrosylation of specific molecular targets is implicated in CNS pathology. S-nitrosylation refers to the post-translational modification of a protein cysteine thiol by NO, forming an endogenous SNO. Because cysteine residues are often key regulators of protein function, S-nitrosylation represents a physiologically important signaling mechanism analogous to other post-translational modifications, such as O-phosphorylation. This article provides an overview of how neurotransmitter NO is produced by nNOS as this represents the most prominent and well defined source of SNO production in the enteric nervous system. Further, it provides a perspective of how S-nitrosylation signals derived from multiple diverse sources may potentially transduce NO bioactivity in the GI tract. Possible lessons that might be learnt from the CNS, such as SNO mediated auto-inhibition of nNOS activity and modulation of neuronal cell death, are also explored as these may have pathophysiological relevance in enteric neuropathy. Thus, S-nitrosylation may mediate previously underappreciated NO-derived signals in the enteric nervous system that regulate homeostatic gut functions and disease susceptibility.
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PMID:S-nitrosothiol signals in the enteric nervous system: lessons learnt from big brother. 2144 85

The enteric nervous system exercises a key role on the gastrointestinal tract (GIT) motility, sensibility, secretions and absorption. This "Little brain of the gut" consists of numerous autonomic neurones located in the GIT, influenced by luminal and intrinsic factors. A new science, the neurogastroenterology, explores the modulation of the GIT functions and the interactions between the central, autonomic and enteric nervous systems forming the brain-gut axis. It works to understand the role of the glial and Cajal's cells, of chemical mediators, hazards of the GIT ontology, influence of inflammation stress and early childhood environment. Motility disorders are congenital or acquired and can persist with more or less severe impairment of quality of life or be a life threatening condition. They are consequences of impaired embryonic development, genetic disorders, systemic diseases, toxic effects, normal or pathologic immunologic reactions acting on the nervous systems or the myocytes. Advances in the understanding of the pathogenesis of uncommon disorders (Hirschsprung disease, achalasia, chronic intestinal pseudo-obstruction) or more prevalent functional disorders (regurgitations, chronic constipation or diarrhoea, functional abdominal pain) contribute to improve the care of such patients. Multidisciplinary team is sometimes mandatory as a holistic approach and the use of sophisticated techniques are important. Improvement of the efficacy of the drugs could by obtained. For clinical works, we need a common language, for this purpose the paediatric Rome III classification of GIT functional disorders is proposed, we need also more consensus on paediatric GI motility exploration protocols.
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PMID:[Neurogastroenterology: focus on pediatric digestive motility diseases]. 2181 95

Nitric oxide (NO), produced by the neural nitric oxide synthase enzyme (nNOS) is a transmitter of inhibitory neurons supplying the muscle of the gastrointestinal tract. Transmission from these neurons is necessary for sphincter relaxation that allows the passage of gut contents, and also for relaxation of muscle during propulsive activity in the colon. There are deficiencies of transmission from NOS neurons to the lower esophageal sphincter in esophageal achalasia, to the pyloric sphincter in hypertrophic pyloric stenosis and to the internal anal sphincter in colonic achalasia. Deficits in NOS neurons are observed in two disorders in which colonic propulsion fails, Hirschsprung's disease and Chagas' disease. In addition, damage to NOS neurons occurs when there is stress to cells, in diabetes, resulting in gastroparesis, and following ischemia and reperfusion. A number of factors may contribute to the propensity of NOS neurons to be involved in enteric neuropathies. One of these is the failure of the neurons to maintain Ca(2+) homeostasis. In neurons in general, stress can increase cytoplasmic Ca(2+), causing a Ca(2+) toxicity. NOS neurons face the additional problem that NOS is activated by Ca(2+). This is hypothesized to produce an excess of NO, whose free radical properties can cause cell damage, which is exacerbated by peroxynitrite formed when NO reacts with oxygen free radicals.
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PMID:The involvement of nitric oxide synthase neurons in enteric neuropathies. 2189 78

Inflammation and immune activation in the gut are usually accompanied by alteration of gastrointestinal (GI) motility. In infection, changes in motor function have been linked to host defense by enhancing the expulsion of the infectious agents. In this review, we describe the evidence for inflammation and immune activation in GI infection, inflammatory bowel disease, ileus, achalasia, eosinophilic esophagitis, microscopic colitis, celiac disease, pseudo-obstruction and functional GI disorders. We also describe the possible mechanisms by which inflammation and immune activation in the gut affect GI motility. GI motility disorder is a broad spectrum disturbance of GI physiology. Although several systems including central nerves, enteric nerves, interstitial cells of Cajal and smooth muscles contribute to a coordinated regulation of GI motility, smooth muscle probably plays the most important role. Thus, we focus on the relationship between activation of cytokines induced by adaptive immune response and alteration of GI smooth muscle contractility. Accumulated evidence has shown that Th1 and Th2 cytokines cause hypocontractility and hypercontractility of inflamed intestinal smooth muscle. Th1 cytokines downregulate CPI-17 and L-type Ca(2+) channels and upregulate regulators of G protein signaling 4, which contributes to hypocontractility of inflamed intestinal smooth muscle. Conversely, Th2 cytokines cause hypercontractilty via signal transducer and activator of transcription 6 or mitogen-activated protein kinase signaling pathways. Th1 and Th2 cytokines have opposing effects on intestinal smooth muscle contraction via 5-hydroxytryptamine signaling. Understanding the immunological basis of altered GI motor function could lead to new therapeutic strategies for GI functional and inflammatory disorders.
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PMID:Cytokine-induced alterations of gastrointestinal motility in gastrointestinal disorders. 2201 52

Neurogastroenterology is defined as neurology of the gastrointestinal tract, liver, gallbladder and pancreas and encompasses control of digestion through the enteric nervous system (ENS), the central nervous system (CNS) and integrative centers in sympathetic ganglia. This Review provides a broad overview of the field of neurogastroenterology, with a focus on the roles of the ENS in the control of the musculature of the gastrointestinal tract and transmucosal fluid movement. Digestion is controlled through the integration of multiple signals from the ENS and CNS; neural signals also pass between distinct gut regions to coordinate digestive activity. Moreover, neural and endocrine control of digestion is closely coordinated. Interestingly, the extent to which the ENS or CNS controls digestion differs considerably along the digestive tract. The importance of the ENS is emphasized by the life-threatening effects of certain ENS neuropathies, including Hirschsprung disease and Chagas disease. Other ENS disorders, such as esophageal achalasia and gastroparesis, cause varying degrees of dysfunction. The neurons in enteric reflex pathways use a wide range of chemical messengers that signal through an even wider range of receptors. These receptors provide many actual and potential targets for modifying digestive function.
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PMID:The enteric nervous system and neurogastroenterology. 2239 90

he occurrence of esophageal and gastric motor dysfunctions happens, when the software of the esophagus and the stomach is injured. This is really a program previously established in the enteric nervous system as a constituent of the newly called neurogastroenterology. The enteric nervous system is composed of small aggregations of nerve cells, enteric ganglia, the neural connections between these ganglia, and nerve fibers that supply effectors tissues, including the muscle of the gut wall. The wide range of enteric neuropathies that includes esophageal achalasia and gastroparesis highlights the importance of the enteric nervous system. A classification of functional gastrointestinal disorders based on symptoms has received attention. However, a classification based solely in symptoms and consensus may lack an integral approach of disease. As an alternative to the Rome classification, an international working team in Bangkok presented a classification of motility disorders as a physiology-based diagnosis. Besides, the Chicago Classification of esophageal motility was developed to facilitate the interpretation of clinical high-resolution esophageal pressure topography studies. This review covers exclusively the medical and surgical management of the esophageal and gastric motor dysfunction using evidence from well-designed studies. Motor control of the esophagus and the stomach, motor esophageal and gastric alterations, treatment failure, side effects of PPIs, overlap of gastrointestinal symptoms, predictors of treatment, burden of GERD medical management, data related to conservative treatment vs. antireflux surgery, and postsurgical esophagus and gastric motor dysfunction are also taken into account.
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PMID:Medical and surgical management of esophageal and gastric motor dysfunction. 2297 33

Chronic disturbances of gastrointestinal function encompass a wide spectrum of clinical disorders that range from common conditions with mild-to-moderate symptoms to rare diseases characterized by a severe impairment of digestive function, including chronic pain, vomiting, bloating and severe constipation. Patients at the clinically severe end of the spectrum can have profound changes in gut transit and motility. In a subset of these patients, histopathological analyses have revealed abnormalities of the gut innervation, including the enteric nervous system, termed enteric neuropathies. This Review discusses advances in the diagnosis and management of the main clinical entities--achalasia, gastroparesis, intestinal pseudo-obstruction and chronic constipation--that result from enteric neuropathies, including both primary and secondary forms. We focus on the various evident neuropathologies (degenerative and inflammatory) of these disorders and, where possible, present the specific implications of histological diagnosis to contemporary treatment. This knowledge could enable the future development of novel targeted therapeutic approaches.
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PMID:New perspectives in the diagnosis and management of enteric neuropathies. 2339 25

Advances in endoscopic submucosal dissection include a submucosal tunneling technique, involving the introduction of tunnels into the submucosa. These tunnels permit safer offset entry into the peritoneal cavity for natural orifice transluminal endoscopic surgery. Technical advantages include the visual identification of the layers of the gut, blood vessels, and subepithelial tumors. The creation of a mucosal flap that minimizes air and fluid leakage into the extraluminal cavity can enhance the safety and efficacy of surgery. This submucosal tunneling technique was adapted for esophageal myotomy, culminating in its application to patients with achalasia. This method, known as per oral endoscopic myotomy, has opened up the new discipline of submucosal endoscopic surgery. Other clinical applications of the submucosal tunneling technique include its use in the removal of gastrointestinal subepithelial tumors and endomicroscopy for the diagnosis of functional and motility disorders. This review suggests that the submucosal tunneling technique, involving a mucosal safety flap, can have potential values for future endoscopic developments.
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PMID:Submucosal tunneling techniques: current perspectives. 2474 23


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