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

Cough is an important defensive reflex of the upper airway and is also a very common symptom of respiratory disease. Cough following an upper respiratory viral infection is transient, and persistent cough is associated with a whole range of conditions, such as asthma, rhino-sinusitis and gastro-oesophageal reflux. Treatment directed at these conditions may improve the associated cough. There is often a need, however, to control cough itself whatever the cause. The most effective drugs in this class are the opioids, such as morphine, codeine or pholcodeine, but at effective doses they have side effects including drowsiness, nausea, constipation and physical dependence. Investigations into the cough reflex and into the potential mechanisms of sensitised cough reflex have uncovered several potential targets for novel drugs. New opioids apart from mu-agonists such as kappa- and delta -receptor agonists, have been developed, in addition to non-opioids such as nociceptin. Neurokinin receptor antagonists, bradykinin receptor antagonists, vanniloid receptor VR-1 antagonists may be beneficial by blocking effects of tachykinins and sensory nerve activation. Local anaesthetics, blockers of sodium-dependent channels and maxi-K Ca2+-dependent channel activators of afferent nerves are inhibitors of the cough reflex. Some of these novel agents may act centrally or peripherally or at both sites as antitussives. Large scale trials of these novel compounds have not been carried out in cough in man but there is a serious need for more effective antitussives devoid of side effects.
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PMID:Cough: potential pharmacological developments. 1208 6

Cough is an important defensive reflex of the upper airway and is also a very common symptom of respiratory disease. Cough after an upper respiratory virus infection is transient, and persistent cough is associated with a whole range of conditions such as asthma, rhino-sinusitis, gastro-oesophageal reflux. Treatment directed at these conditions may improve the associated cough. There is often a need, however, to control cough itself, whatever the cause. The most effective drugs in this class are the opioids, such as morphine, codeine or pholcodeine, but at effective doses they have side-effects such as drowsiness, nausea, constipation and physical dependence. Investigations into the cough reflex and into the potential mechanisms of sensitised cough reflex have uncovered several potential targets for novel drugs. New opioids such as k- and d-receptor agonists apart from m-agonists have been developed, in addition to non-opioid, nociceptin. Neurokinin receptor antagonists, bradykinin receptor antagonists, vanilloid receptor VR-1 antagonists may be beneficial by blocking effects of tachykinins, and sensory nerve activation. Local anaesthetics, blockers of sodium-dependent channels, and maxi-K CA2+-dependent channel activators of afferent nerves are inhibitors of the cough reflex. Some of these novel agents may act centrally or peripherally or at both sites as antitussives. Large scale trials of these novel compounds have not been tried in cough in man, but there is a serious need for more effective antitussives devoid of side-effects.
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PMID:Therapy for cough: active agents. 1209 88

The association between asthma and gastroesophageal reflux has been attributed to microaspiration of gastric contents and/or vagally mediated reflex bronchoconstriction. In previous experimental studies concerning the pulmonary effects of tracheal or esophageal acid infusion, only animals without airway inflammation have been studied. We assessed the effects of esophageal and tracheal administration of hydrochloric acid (HCl) on normal guinea pigs (GP) and GP with airway inflammation induced by repeated ovalbumin exposures. These GP were anesthetized (pentobarbital sodium) and received 1) 20 microl of either 0.2 N HCl or saline into the trachea, or 2) 1 ml of either 1 N HCl or saline into the esophagus. Intratracheal HCl resulted in a significant increase in both respiratory system elastance and resistance (P < 0.001). There were no significant changes in respiratory mechanics when HCl was infused into the esophagus. In conclusion, we observed that infusion of large volumes of HCl into the esophagus did not change pulmonary mechanics significantly, even in guinea pigs with chronic allergen-induced airway inflammation. In contrast, intratracheal administration of small amounts of acid had substantial effects in normal GP and GP with airway inflammation.
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PMID:Pulmonary responses to tracheal or esophageal acidification in guinea pigs with airway inflammation. 1218 76

Gastroesophageal reflux disease (GERD) is associated with several symptoms, such as heartburn, belching, and regurgitation, which arise from esophageal exposure to gastric acid. Symptoms may occur in the absence of endoscopically observed esophageal mucosal damage and inflammation. These patients represent the majority of those who present with GERD symptoms. Although acid suppression therapy is a logical approach to relieving GERD symptoms, it has been thought to relieve symptoms less reliably in patients with endoscopically negative, or symptomatic GERD than in those with erosive GERD. Two multicenter, randomized, double-blind, placebo-controlled clinical trials were conducted in the United States to evaluate the efficacy of rabeprazole sodium 10 mg and 20 mg compared with placebo for the relief of heartburn and other symptoms associated with symptomatic GERD. Results from these studies indicated that rabeprazole 10 or 20 mg once daily relieved heartburn within the first 1 or 2 days of treatment and also had significant positive effects on other GERD symptoms, including regurgitation, belching, bloating, satiety, and nausea. Overall, these results suggest that rabeprazole may hold a significant therapeutic advantage in the treatment of heartburn and other symptoms associated with endoscopically negative GERD, particularly in the majority of patients who often are treated empirically without, or before, endoscopic evaluation.
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PMID:Rabeprazole-based therapy in the management of symptomatic gastroesophageal reflux disease. 1264 31

Cough is an important defensive reflex of the airway and a common symptom of respiratory disease. After an upper respiratory tract virus infection, cough is transient, but is more persistent with conditions such as asthma, rhinosinusitis, gastroesophageal reflux, chronic obstructive pulmonary disease (COPD) and lung cancer. Treatment directed at these conditions may improve cough, but there remains a need to control cough directly. The most effective antitussives are opioids, such as morphine, codeine or pholcodeine, but they produce side effects including drowsiness, nausea, constipation and physical dependence. Opioids such as k- and d-opioid receptor agonists, non-opioids such as nociceptin, neurokinin and bradykinin receptor antagonists, vanilloid receptor VR(1) antagonists, blockers of sodium-dependent channels, and maxi-K calcium-dependent channel activators of afferent nerves may all represent novel antitussives and this needs to be confirmed in clinical trials.
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PMID:Current and future prospects for drugs to suppress cough. 1291 74

Abnormal gastro-oesophageal reflux and bile acids have been linked to the presence of Barrett's oesophageal premalignant lesion associated with an increase in mucin-producing goblet cells and MUC4 mucin gene overexpression. However, the molecular mechanisms underlying the regulation of MUC4 by bile acids are unknown. Since total bile is a complex mixture, we undertook to identify which bile acids are responsible for MUC4 up-regulation by using a wide panel of bile acids and their conjugates. MUC4 apomucin expression was studied by immunohistochemistry both in patient biopsies and OE33 oesophageal cancer cell line. MUC4 mRNA levels and promoter regulation were studied by reverse transcriptase-PCR and transient transfection assays respectively. We show that among the bile acids tested, taurocholic, taurodeoxycholic, taurochenodeoxycholic and glycocholic acids and sodium glycocholate are strong activators of MUC4 expression and that this regulation occurs at the transcriptional level. By using specific pharmacological inhibitors of mitogen-activated protein kinase, phosphatidylinositol 3-kinase, protein kinase A and protein kinase C, we demonstrate that bile acid-mediated up-regulation of MUC4 is promoter-specific and mainly involves activation of phosphatidylinositol 3-kinase. This new mechanism of regulation of MUC4 mucin gene points out an important role for bile acids as key molecules in targeting MUC4 overexpression in early stages of oesophageal carcinogenesis.
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PMID:Transcriptional regulation of human mucin MUC4 by bile acids in oesophageal cancer cells is promoter-dependent and involves activation of the phosphatidylinositol 3-kinase signalling pathway. 1458 90

A 2 month old female infant presented an aphonic voice and increasing inspiratory stridor due to a stenosing granulating laryngitis. A pathologically elevated gastroesophageal reflux was measured by means of 24-h pH-metry. After antireflux therapy (Cisaprid, sodium alginate and upright body positioning), the laryngitis was completely healed. This case confirms that an elevated gastroesophageal reflux in infants can cause chronic inflammatory diseases of the upper respiratory tract, especially of the larynx.
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PMID:[Stenosing gastric laryngitis in infancy]. 1502 69

Barrett's oesophagus is an acquired precancerous condition that develops from mucosal injury incurred due to chronic gastro-oesophageal reflux. The aim of this study was to determine if bile and/or acid components of the refluxate can induce DNA damage in vitro. The oesophageal cell lines FLO-1 and HET1-A were exposed to primary bile salts, individually or as a mixture, and the secondary bile salt sodium deoxycholate, in neutral or acidified media. Cells were then examined in the comet assay to measure DNA strand breaks. Cell viability was also monitored. Acidified media induced DNA damage in a pH- and time-dependent manner. The primary bile compounds sodium glycocholate, glycocholic acid, sodium taurocholate and taurochenodeoxycholate, as an equimolar mixture (100 microM), caused a small but significant (P < 0.028) elevation in DNA damage, but only at neutral pH in FLO-1 cells. Sodium deoxycholate (100 microM) caused a significant (P < 0.008) elevation in DNA damage in both cell lines, but again only at neutral pH. These data suggest that specific components of gastro-oesophageal refluxate are capable of causing DNA damage and may participate in the genesis and progression of Barrett's oesophagus via this mechanism.
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PMID:Acid and bile salts induce DNA damage in human oesophageal cell lines. 1521 32

Santarus Inc. is developing an immediate-release formulation of omeprazole in combination with an antacid (sodium bicarbonate) as a powder for suspension, known as Acitreltrade mark [SAN 05] and also as Rapinex powder for oral suspension. This omeprazole powder suspension will be used to treat gastrointestinal haemorrhage, gastro-oesophageal reflux disease, heartburn and peptic ulcers. Acitreltrade mark is based on technology licensed from the University of Missouri. Santarus have also licensed technology from Tulane and North Carolina Universities relating to potential treatments for gastrointestinal (GI) diseases. Santarus has licensed exclusive, worldwide rights to patent applications covering specific combination formulations of proton pump inhibitors (PPIs) and antacids for treating various upper GI diseases and disorders. Santarus plans to license the development, distribution and marketing rights of omeprazole powder for oral suspension 20 mg outside the US, to one or more well established pharmaceutical companies. The US FDA has requested that Santarus pursue a name other than Rapinex for the product. Santarus is currently discussing potential alternative names for the product with the FDA. Santarus announced positive results in August 2003 from a phase III trial comparing oral Acitrel (Rapinex 40 mg) with intravenous cimetidine in preventing upper GI bleeding in 359 critically ill adult patients. Santarus has also completed an open-label clinical trial in 243 patients, including 97 patients with gastric ulcers, evaluating the safety of this omeprazole 40 mg powder suspension for an 8-week period. In connection with the NDA for omeprazole powder suspension 40 mg, Santarus provided notice to the NDA holder for Prilosec delayed-release capsules and related patent owners that omeprazole powder suspension 40 mg does not infringe currently listed patents for Prilosec or that those patents are invalid.
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PMID:Omeprazole/Antacid-powder suspension-Santarus: omeprazole/sodium bicarbonate powder-Santarus, SAN 05. 1556 39

Cough is an important defensive reflex of the airway and also a common symptom of respiratory disease. Cough after common respiratory virus infection is transient but is more persistent when associated with conditions such as asthma, rhinosinusitis, gastro-oesophageal reflux, chronic obstructive pulmonary disease and lung cancer. Persistent cough may be due to peripheral and/or central sensitisation of cough reflexes initiated by cough receptors, rapidly adapting receptors or nociceptors. Treatment directed at associated conditions such as asthma (with anti-inflammatories) and gastro-oesophageal reflux (with proton-pump inhibitors) improve cough. There remains a need to use drugs that suppress the neural activity of cough (termed nonspecific), as treatments directed at the clinical cause(s) of the underlying cough (termed specific) may not be effective. The most effective indirect antitussives are opioids such as morphine, codeine or pholcodeine, but they produce side effects such as drowsiness, nausea, constipation and physical dependence. Opioids such as kappa- and delta-receptor agonists, non-opioids such as nociceptin, neurokinin and bradykinin receptor antagonists, cannabinoids, vanilloid receptor-1 antagonists, blockers of Na+-dependent channels, and large conductance Ca2+-dependent K+-channel activators of afferent nerves may represent novel antitussives.
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PMID:Drugs to suppress cough. 1570 18


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