Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0017168 (gastroesophageal reflux disease)
 11,783 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Vagal afferents are extensively distributed in the digestive tract from the oesophagus to the colon. They are involved in the reflex control of normal gastrointestinal (GI) tract function (e.g. secretion and motility) as well as reflexes more characteristic of diseases such as functional dyspepsia and gastroesophageal reflux disease (e.g. vomiting, disordered lower esophageal sphincter relaxation and gastric accommodation). They are also implicated in signalling non-painful sensations (e.g. nausea and early satiety) associated with disease. A variety of receptors has been identified on vagal afferents, which can either enhance (e.g. 5-HT3, CCK1, VR1 and NK1 receptors) or reduce (e.g. ghrelin, leptin, k-opioid and GABAB receptors) activity, offering a range of potential therapeutic targets. Commonly used laboratory species (e.g. rat and mouse) lack an emetic reflex, and the implications of this for models of upper GI disorders have been explored in the light of expanding knowledge of the neuropharmacology of the emetic reflex implicating glutamate, prostanoids, cannabinoids and substance P. Additional pathophysiological roles for vagal afferents (e.g. in thermoregulation, arousal and fatigue) are being investigated, raising the intriguing possibility of the vagus as a target in non-GI disorders.
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PMID:Abdominal vagal afferent neurones: an important target for the treatment of gastrointestinal dysfunction. 1248 26

Gastrointestinal malignancies may be associated with obesity, defined specifically by increased body-mass index, and based largely on environmental factors rather than genetics. In particular, there seems to be a definite increase in the incidence of both oesophageal and colorectal cancer. Mechanisms associated with obesity include a particular metabolic state characterized by hyperinsulinemia, or insulin resistance, along with elevated serum leptin. Leptin is derived from adipocytes and appears to play a role in the regulation of ghrelin, a peptide derived from the stomach and small intestine that stimulates appetite and weight gain. In addition to these metabolic changes, there are other anatomical alterations that may indirectly predispose to cancer, including the predisposition of obesity to gastroesophageal reflux and, possibly, oesophageal cancer. Other mechanisms may involve adipocyte-derived cytokines, or adipokines, that may serve as signalling devices in the pathogenesis of cancer. Finally, pharmacologic and surgical avenues available for treatment of obesity, including lipase inhibitors and gastric or jejuno-ileal bypass procedures may set the stage for subsequent gastric or intestinal tract cancer.
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PMID:Risk of gastrointestinal malignancies and mechanisms of cancer development with obesity and its treatment. 1556 45

The incidence and prevalence of gastro-oesophageal reflux disease is rising. Changing dietary habits and increasing body weight can be held responsible. In several studies a close relation was found between body weight and the occurrence of reflux disease. It may be concluded that there is a definite relation between body mass index and the occurrence of reflux disease. H. pylori probably also plays a role. H. pylori causes changes in fundic leptin levels and plasma levels of ghrelin. Eradication of H. pylori infection can increase appetite leading to a rise in body mass index due to a higher caloric intake. H. pylori can be a 'protective' factor against the development of overweight. Since only a minority of overweight or obese patients with gastro-oesophageal reflux disease will lose weight successfully, medical treatment with effective acid suppression will be the mainstay of the treatment of reflux disease in patients with a high body mass index.
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PMID:Helicobacter pylori, obesity and gastro-oesophageal reflux disease. Is there a relation? A personal view. 1699 Jun 98

Gastrointestinal (GI) motility has a crucial role in the food consumption, digestion and absorption, and also controls the appetite and satiety. In obese patients, various alterations of GI motility have been investigated. The prevalence of GERD and esophageal motor disorders in obese patients are higher than those of general population. Gastric emptying of solid food is generally accelerated and fasting gastric volume especially in distal stomach is larger in obese patients without change in accommodation. Contractile activity of small intestine in fasting period is more prominent, but orocecal transit is delayed. Autonomic dysfunction is frequently demonstrated in obese patients. These findings correspond with increased appetite and delayed satiety in obese patients, but causes or results have not been confirmed. Therapeutic interventions of these altered GI motility have been developed using botulinum toxin, gastric electrical stimulation in obese patients. Novel agents targeted for GI hormone modulation (such as ghrelin and leptin) need to be developed in the near future.
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PMID:[Obesity and gastrointestinal motility]. 1692 52

The past 20 years have seen notable advances in our understanding of the physiology and pharmacology of the emetic reflex leading to the identification of the anti-emetic effects of 5-hydroxytryptamine(3) (5-HT(3)) and neurokinin(1) receptor (NK(1)) antagonists. The introduction of 5-HT(3) and NK(1) receptor antagonists into the clinic has had a major impact in alleviating the nausea and vomiting associated with the treatment of cancer and the sequelae to anaesthesia and surgery (post-operative nausea and vomiting, PONV). Despite these advances there are major gaps in our understanding. Interestingly, one of these is the relatively poor ability to treat nausea. Additional gaps in our knowledge are highlighted to provide a framework within which directions for research can be proposed. Particular attention is drawn to: lacunae in knowledge of some currently used anti-emetics such as the source of dopamine required to initiate emesis; the theoretical assumptions and mechanisms underlying the concept of a "universal anti-emetic"; the variety of receptors at which agonists act to have anti-emetic effects (GABA (B), CB(1), 5-HT(1A), ghrelin, opioid); issues of translation from animals to humans and the relationship between the pathways involved in emesis and certain gastrointestinal disorders such as dyspepsia and gastroesophageal reflux, with the latter being of particular interest as some agents affecting reflux are also anti-emetic. Together, the unmet clinical need to adequately control nausea, possibly by new drugs acting within the brainstem, and the significant gaps in understanding key aspects of the emetic reflex, suggest an important need to focus and re-direct research into the distressing and sometimes life-threatening symptoms of nausea and vomiting.
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PMID:Treatment of nausea and vomiting: gaps in our knowledge. 1693 36

Gastroesophageal reflux disease (GERD) refers to the very common and constantly increasing conditions where reflux of gastric contents into the esophagus leads to development of characteristic symptoms. The esophagus, LES and stomach can be envisioned as single functional unit controlled by neuro-hormonal factors. The abnormalities that contribute to GERD can start in any component of this unit, resulting particularly from disturbances in their control system. It is extremely important to identify factors and mechanisms leading to functional failure of this system so that causative therapy can be effectively applied. The key-role has been attributed to parasympathetic dysfunction, which may adversely affect motor activity of this area by increasing transient LES relaxation number and impairing LES pressure, esophageal acid clearance and motility of the proximal stomach. Recently, numerous investigations have been performed to elucidate the role of Helicobacter pylori (Hp) infection in GERD pathogenesis with the most concern given to its potency to increase gastric acid secretion. However, it appeared that this infection leads to much more complex changes in gastric mucosa including modification of afferent neural signals and specific gastric hormones release. Plasma ghrelin level is low in subjects infected and increases significantly after eradication. Since ghrelin, beside potency to increase gastric secretion has strong prokinetic action on LES functional unit, this phenomenon together with impaired vagal control may contribute to the Hp infection or eradication - related GERD development. Thus, ghrelin and vagal activity could be the missing links that partially explains relationship between GERD and Hp infection.
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PMID:Helicobacter pylori infection in pathogenesis of gastroesophageal reflux disease. 1703 7

Traditional Japanese medicine (Kampo) is used to treat various disorders of the gastrointestinal tract in Japan, where it is fully integrated into the modern healthcare system. Recently, scientific research on herbal medicine in Japan has been reported in English journals. The objective of the current review is to introduce two traditional Japanese medicines and to provide evidenced-based information regarding their use. Daikenchuto, which consists of three different herbs, is the most frequently prescribed traditional Japanese medicine in Japan. Daikenchuto stimulates gastrointestinal motility though a neural reflex involving presynaptic cholinergic and 5-HT3 receptors. Daikenchuto improves postoperative bowel motility and postoperative ileus. Furthermore, it is reported to cause an increase in gastrointestinal hormones (motilin, vasoactive intestinal peptide, and calcitonin gene-related peptide) and intestinal blood flow. Rikkunshito, a traditional Japanese medicine consisting of eight herbs, is thought to stimulate gastrointestinal motility and ghrelin secretion. Rikkunshito is effective for improving the symptoms of functional dyspepsia, gastroesophageal reflux disease, and cisplatin-induced anorexia and vomiting. Traditional Japanese medicine has the potential to be used successfully in the treatment of gastrointestinal disorders. Details regarding the physiological and clinical effects of traditional Japanese medicine must be further examined in order to become more widely accepted in other countries.
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PMID:The effect of traditional Japanese medicine (Kampo) on gastrointestinal function. 2111 Jan 52

Circadian and seasonal rhythms are a fundamental feature of all living organisms and their organelles. Biological rhythms are responsible for daily food intake; the period of hunger and satiety is controlled by the central pacemaker, which resides in the suprachiasmatic nucleus (SCN) of the hypothalamus, and communicates with tissues via bidirectional neuronal and humoral pathways. The molecular basis for circadian timing in the gastrointestinal tract (GIT) involves interlocking transcriptional/translational feedback loops which culminate in the rhythmic expression and activity of a set of clock genes and related hormones. Interestingly, it has been found that clocks in the GIT are responsible for the periodic activity (PA) of its various segments and transit along the GIT; they are localized in special interstitial cells, with unstable membrane potentials located between the longitudinal and circular muscle layers. The rhythm of slow waves is controlled in various segments of the GIT: in the stomach (about 3 cycles per min), in the duodenum (12 cycle per min), in the jejunum and ileum (from 7 to 10 cycles per min), and in the colon (12 cycles per min). The migrating motor complex (MMC) starts in the stomach and moves along the gut causing peristaltic contractions when the electrical activity spikes are superimposed on the slow waves. GIT hormones, such as motilin and ghrelin, are involved in the generation of MMCs, while others (gastrin, ghrelin, cholecystokinin, serotonin) are involved in the generation of spikes upon the slow waves, resulting in peristaltic or segmental contractions in the small (duodenum, jejunum ileum) and large bowel (colon). Additionally, melatonin, produced by neuro-endocrine cells of the GIT mucosa, plays an important role in the internal biological clock, related to food intake (hunger and satiety) and the myoelectric rhythm (produced primarily by the pineal gland during the dark period of the light-dark cycle). This appears to be an endocrine encoding of the environmental light-dark cycle, conveying photic information which is used by organisms for both circadian and seasonal organization. Motor and secretory activity, as well as the rhythm of cell proliferation in the GIT and liver, are subject to many circadian rhythms, mediated by autonomic cells and some enterohormones (gastrin, ghrelin and somatostatin). Disruption of circadian physiology, due to sleep disturbance or shift work, may result in various gastrointestinal diseases, such as irritable bowel syndrome (IBS), gastroesophageal reflux disease (GERD) or peptic ulcer disease. In addition, circadian disruption accelerates aging, and promotes tumorigenesis in the liver and GIT. Identification of the molecular basis and role of melatonin in the regulation of circadian rhythm allows researchers and clinicians to approach gastrointestinal diseases from a chronobiological perspective. Clinical studies have demonstrated that the administration of melatonin improves symptoms in patients with IBS and GERD. Moreover, our own studies indicate that melatonin significantly protects gastrointestinal mucosa, and has strong protective effects on the liver in patients with non-alcoholic steatohepatitis (NASH). Recently, it has been postulated that disruption of circadian regulation may lead to obesity by shifting food intake schedules. Future research should focus on the role of clock genes in the pathophysiology of the GIT and liver.
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PMID:Gut clock: implication of circadian rhythms in the gastrointestinal tract. 2167 61

The speculations on the protective role of Helicobacter pylori against gastroesophageal reflux disease (GERD) originated from epidemiological observations. These studies have shown that the rising trend of GERD is coincident with declining prevalence of H. pylori and peptic ulcer disease in Asia. Furthermore, most case-control and population-based studies suggest a negative association between H. pylori infection and GERD. It is generally believed that the preponderance of cagA+ and vacA+ virulent strains and proinflammatory interleukin-1 beta polymorphism increase the risk of hypochlohydria and protects against the development of GERD in Asian population. Recovery of gastric acid secretion and emergence of reflux esophagitis has been reported after H. pylori eradication in patients with corpus gastritis and atrophic gastritis. Recent studies have also reported that H. pylori eradication leads to recovery of ghrelin secreting cells in the gastric corpus and a rise in plasma ghrelin levels, which may contribute to obesity through its appetite-stimulating action and predispose to GERD. The prevalence of H. pylori infection is generally lower in younger Asians who enjoy improved socioeconomic status and sanitation compared with their older counterparts. The Asian population is probably facing a rising generation with high gastric acid and ghrelin secretion rates. These physiological changes may contribute to increased dietary calorie intake, obesity and increased prevalence of GERD.
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PMID:Does Helicobacter pylori infection protect against esophageal diseases in Asia? 2187 Jan 39

Research published over the past year has documented the continued decline of Helicobacter pylori-related peptic ulcer disease and increased recognition of non-H. pylori, non-steroidal anti-inflammatory drugs ulcer disease--idiopathic ulcers. Despite reduced prevalence of uncomplicated PUD, rates of ulcer complications and associated mortality remain stubbornly high. The role of H. pylori in functional dyspepsia is unclear, with some authors considering H. pylori-associated nonulcer dyspepsia a distinct organic entity. There is increasing acceptance of an inverse relationship between H. pylori and gastroesophageal reflux disease (GERD), but little understanding of how GERD might be more common/severe in H. pylori-negative subjects. Research has focused on factors such as different H. pylori phenotypes, weight gain after H. pylori eradication, and effects on hormones such as ghrelin that control appetite.
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PMID:Helicobacter pylori and nonmalignant diseases. 2189 83


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