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

Metabolic syndrome is a cluster of metabolic abnormalities consisting essentially of obesity, especially abdominal obesity. Metabolic syndrome has been highlighted as a risk factor for cardiovascular and other chronic diseases. Obesity has been implicated in various gastrointestinal diseases such as gastroesophageal reflux diseases and colorectal cancer. Recently, abdominal obesity has been shown to be more important than obesity as expressed by an elevated body mass index as a causative factor for the development of these diseases. In addition to the mechanical effects of obesity, such as an increase in intra-abdominal pressure from large amounts of adipose tissue, substances that adipose tissues secrete, such as tumor necrosis factor-alpha, interleukin-6, leptin, and insulin-like growth factor-1, have been proposed to be pathogenic links to these diseases. In this review, we discuss the association of metabolic syndrome or the individual components of metabolic syndrome, focusing on obesity and abdominal obesity, with gastrointestinal diseases.
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PMID:Metabolic syndrome and gastrointestinal diseases. 1746 54

Obesity and gastro-oesophageal reflux are the main predisposing factors for oesophageal adenocarcinoma. We have examined the effects of transient acid exposure and leptin on OE33 oesophageal adenocarcinoma cells. Leptin and acid individually stimulated proliferation and inhibited apoptosis and the combination was synergistic. Leptin receptor protein levels were unchanged by acid exposure. The COX-2 inhibitor NS 398 blocked the effects of acid and leptin but while both acid and leptin individually significantly increased PGE2 production and COX-2 mRNA levels, the combination was not more effective than either stimulant alone. Leptin synergistically enhanced acid-stimulated EGFR and ERK phosphorylation but did not further increase JNK or p38 MAP kinase phosphorylation. Specific EGFR and ERK inhibitors reduced the effects of leptin and acid alone and in combination. The combination of increased circulating leptin levels in obesity and transient reflux of gastric acid may promote oesophageal carcinogenesis by increasing proliferation and inhibiting apoptosis.
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PMID:Leptin synergistically enhances the anti-apoptotic and growth-promoting effects of acid in OE33 oesophageal adenocarcinoma cells in culture. 1761 45

Epidemiologic data indicate that obesity increases the prevalence and incidence of asthma and reduces asthma control. Obese mice exhibit innate airway hyperresponsiveness and augmented responses to certain asthma triggers, further supporting a relationship between obesity and asthma. Here I discuss several mechanisms that may explain this relationship. In obesity, lung volume and tidal volume are reduced, events that promote airway narrowing. Obesity also leads to a state of low-grade systemic inflammation that may act on the lung to exacerbate asthma. Obesity-related changes in adipose-derived hormones, including leptin and adiponectin, may participate in these events. Comorbidities of obesity, such as dyslipidemia, gastroesophageal reflux, sleep-disordered breathing, type 2 diabetes, or hypertension may provoke or worsen asthma. Finally, obesity and asthma may share a common etiology, such as common genetics, common in utero conditions, or common predisposing dietary factors. Novel therapeutic strategies for treatment of the obese patient with asthma may result from an increased understanding of the mechanisms underlying this relationship.
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PMID:Obesity and asthma: possible mechanisms. 1840 59

Obesity has been associated with an increased prevalence of asthma and poorer control of this disease. However, the mechanisms by which obesity can influence airway function and make asthma more difficult to control remain uncertain. The physiological changes associated with obesity can contribute to respiratory symptoms and these should be differentiated from those caused by asthma. Obesity can possibly influence the development of asthma through genetic, developmental, hormonal, neurogenic or mechanical influences. Breathing at low lung volumes and changes in the pattern of breathing in obese subjects may alter airway smooth muscle plasticity and airway function. The release by adipocytes of various cytokines and mediators such as Interleukin-6, TNF-alpha, eotaxin, and leptin, and the reduction of anti-inflammatory adipokines in obese subjects may possibly contribute to the development or increased clinical expression of asthma in promoting airway inflammation. Reduced asthma control and impaired response to asthma therapy have been reported in obese patients. Obesity-related co-morbidities such as Sleep Apnea and Gastro-esophageal reflux may also contribute to this poor control. Weight loss improves asthma control and reduces medication needs. Research is needed to better define the optimal management of obese asthmatic patients.
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PMID:Influence of obesity on the prevalence and clinical features of asthma. 1903 10

Recent data suggest that obstructive sleep apnea syndrome (OSAS) is an independent risk factor for asthma exacerbations. Neuromechanical reflex bronchoconstriction, gastroesophageal reflux, inflammation (local and systemic), and the indirect effect on dyspnea of OSAS-induced cardiac dysfunction have been suggested as mechanisms that lead to worsening asthma control in patients with concomitant OSAS. Vascular endothelial growth factor-induced airway angiogenesis, leptin-related airway changes, and OSAS-induced weight gain also may play a common mechanistic role linking both disorders. Several studies have confirmed that asthmatic patients are more prone to develop OSAS symptoms than are members of the general population. The common asthmatic features that promote OSAS symptoms are nasal obstruction, a decrease in pharyngeal cross sectional area, and an increase in upper airway collapsibility. Clarifying the nature of the relationship between OSAS and asthma is a critical area with important therapeutic implications.
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PMID:Obstructive sleep apnea syndrome and asthma: what are the links? 1931 86

Obesity and asthma prevalence have been increasing over the past decade. Epidemiological evidence demonstrates that obesity results in an increased risk of developing incident asthma. Even modest levels of increased weight increase asthma risk. Recently published data suggest that obese asthma patients may represent a distinct phenotype of asthma. Obese asthma patients demonstrate increased asthma severity, as indicated by increased exacerbations and decreased asthma control; however, they do not appear to have increased airway cellular inflammation. It seems likely that obesity does not contribute to asthma through conventional Th type 2-mediated inflammatory pathways but, rather, through separate mechanisms that are specific to the obese state. This may explain the variable responses of obese asthma patients to conventional asthma therapies, specifically, relative corticosteroid resistance. Small studies suggest improvements in the disease with weight loss in obese asthma patients, and other interventions to target asthma in obese individuals need to be investigated. Several postulated mechanisms for the occurrence of this distinct phenotype have been postulated: 1) the presence of comorbidities, such as gastroesophageal reflux disease and sleep disordered breathing, 2) systemic inflammation associated with obesity (with elevated levels of circulating cytokines, such as IL-6 and TNF-alpha), 3) increased oxidative stress, and 4) hormones of obesity, such as adiponectin, leptin, and resistin. Although the mechanisms underlying obesity in asthma require further investigation, obesity plays a major role in the asthma epidemic and likely results in a distinct phenotype of the disease.
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PMID:Does obesity produce a distinct asthma phenotype? 1987 8


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