Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0847097 (acidity)
 15,165 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Gastro-oesophageal reflux disease (GERD) covers a broad range of signs and symptoms arising from the orad movement of gastric contents into the oesophagus, oropharynx, larynx or airway. Most commonly, contact with and damage to the oesophageal epithelium by acidic refluxate causes micro or macroscopic defects leading to the symptom of heartburn. However, GERD can also give rise to extra-oesophageal manifestations such as pharyngitis, laryngitis, asthma and other disorders, identifiable as acid-mediated events by a favorable response to acid suppression. Only one-third of individuals with heartburn have endoscopic evidence of erosive oesophagitis; the remainder have endoscopy-negative or non-erosive reflux disease (NERD). Improved investigative technologies are increasing our understanding of the pathophysiology of NERD. For example, although a number of microscopic abnormalities have been identified, oesophageal damage in NERD has been shown to be characterized by the presence of 'dilated intercellular spaces' within oesophageal stratified squamous epithelium. Dilated intercellular spaces that reflect damage to the intercellular junctions enable levels of acidity that would be considered innocuous when present in the oesophageal lumen to initiate pathological responses within oesophageal nociceptors when present within the intercellular spaces. This effectively gives rise to the symptom of heartburn. Excessive acidity within the intercellular spaces in NERD also presages its evolution to erosive disease, the latter through inflammation-mediated disruption of the antireflux and luminal clearance mechanisms. Support for this scenario is evident by the ability of effective acid control with proton pump inhibitors both to control symptoms, and lead to resolution of dilated intercellular spaces in patients with both erosive and non-erosive disease. This article examines these concepts and how they shape our current understanding of GERD.
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PMID:Current understanding of the mechanisms of gastro-oesophageal reflux disease. 1686 42

Proton pump inhibitor (PPI) therapy is widely used in the management of patients with ulcer bleeding. However, most randomized controlled trials (RCTs) have been conducted outside of the United States. Jensen and colleagues have conducted the first United States-based RCT to compare a PPI with an H(2)-receptor antagonist following appropriate endoscopic hemostatic treatment for patients with ulcer bleeding. Unfortunately, the trial had to be discontinued prematurely because of problems with enrolment. There was a statistically nonsignificant difference in rebleeding rates between the two treatment arms. A type II statistical error probably explains this apparent lack of efficacy. However, U.S. patients may also require higher doses of PPI for adequate control of intragastric acidity.
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PMID:To establish the efficacy of PPI therapy for ulcer bleeding in the United States, do we need more patients or more PPI [corrected]. 1696 4

Oxynticopeptic cells of fish stomach are thought to secrete less acid than the specialized parietal cells of mammalian stomach. Gastric acidity, however, has not been directly compared between fish and mammals. We therefore fed rainbow trout and rats the same meal, and found that the lowest postprandial pH of trout stomach was 2.7, which was only transiently sustained for 1 h, whereas that of rat stomach was 1.3, which was sustained for 3 h. Postprandial pH of the small intestine was slightly higher in trout (approximately 8.0) than in rats (approximately 7.6), but pH of the large intestine was similar (approximately 8.0). Addition of acids to fish feeds, in an attempt to aid the weak acidity of fish stomach, has been known to improve phosphorus digestibility, but its physiological effect on fish stomach is not known. Exogenous acids did improve phosphorus digestibility but also decreased steady-state mRNA expression of trout H(+)/K(+)-ATPase (ATP4A, the proton pump) as well as Na(+)/bicarbonate cotransporter (NBC), and had no effect on gastrin-like mRNA and somastostatin (SST) mRNA abundance. Gastrin-like mRNA and SST-2 mRNA were equally distributed between corpus and antrum. ATP4A mRNA and NBC mRNA were in the corpus, whereas SST-1 mRNA was in the antrum. Trout gastrin-like EST had modest homology to halibut and pufferfish gastrin, whereas trout ATP4A mRNA had > or = 95% amino acid homology with mammalian, Xenopus and flounder ATP4A. Although ATP4A seems highly conserved among vertebrates, gastric acidity is much less in trout than in rats, explaining the low digestibility of bone phosphorus, abundant in fish diets. Dietary acidification does not reduce acidity enough to markedly improve phosphorus digestibility, perhaps because exogenous acids may inhibit endogenous acid production.
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PMID:Dietary acidification enhances phosphorus digestibility but decreases H+/K+-ATPase expression in rainbow trout. 1698 89

Critically ill patients are at risk to develop stress ulceration of the gastric mucosa. Although the evidence for efficacity of specific medications to prevent stress ulcer is discordant, there is general agreement in favor of prophylaxis to prevent stress ulceration in patients at high risk - i.e., surgical patients in the ICU setting with mechanical ventilation, anticoagulation, or instability. Although no medication is specifically authorized in France for this indication, H2 blockers and proton pump inhibitors (PPI's) are generally the agents of choice. While PPI's are the most potent inhibitors of gastric acidity, no evidence exists to prove their superior efficacity. Numerous questions remain unanswered (which drug? at what dose? for how long?) which underline the need to develop intra-institutional consensus.
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PMID:[Prevention of stress ulcer: A practical approach]. 1708 25

This work assessed the mechanism underlying the antisecretory gastric acid effect of Plectranthus barbatus Andrews (Lamiaceae) and active constituents. Popularly known as "false-boldo", this plant is used in Brazilian folk medicine to treat gastrointestinal and hepatic ailments. The plant aqueous extract (AE) and isolated compounds were assayed in vivo in pylorus-ligated mice, and in vitro on acid secretion measured as [(14)C]-aminopyrine ([(14)C]-AP) accumulation in rabbit gastric glands and gastric H(+),K(+)-ATPase preparations. Injected into the duodenal lumen, the AE of the plant leaves (0.5 and 1.0 g/kg) decreased the volume (62 and 76%) and total acidity (23 and 50%) of gastric acid secretion in pylorus-ligated mice. Bioguided purification of the AE yielded an active fraction (IC(50)=24 microg/ml) that inhibited acid secretion in rabbit gastric glands with a potency 10 to 18 times greater than that of the originating extract, on both the basal and stimulated acid secretion by histamine (His) (1 microM) or bethanechol (100 microM). At the same concentrations the gastric H(+),K(+)-ATPase activity was also inhibited. The active constituent was chemically identified as the abietanoid dienedione plectrinone A which reduced the H(+),K(+)-ATPase activity with IC(50)=171 microM. The results indicate that inhibition of the gastric proton pump by this diterpenoid may account for the antisecretory acid effect and reputed anti ulcer activity of Plectranthus barbatus.
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PMID:Inhibition of the gastric H+,K+ -ATPase by plectrinone A, a diterpenoid isolated from Plectranthus barbatus Andrews. 1716 78

Chronic idiopathic singultus (hiccup) is a debilitating condition affecting mostly elderly males. While in the past, pharmacologic singultus treatment was mostly "trial and error," more recently, treatment has become both more evidence based and pathophysiology guided. A combination of an acidity-reducing drug (H(2)-receptor blocker or proton pump inhibitor) with baclofen (gamma-amino-butyric-acid receptor type B agonist) has become the most widely used regimen. Some clinicians replace or supplement baclofen with gabapentin. We present three cases of chronic idiopathic hiccup managed with gabapentin or another alpha-2-delta ligand, pregabalin. This is the first reported use of pregabalin for this indication.
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PMID:Alpha-2-delta ligands for singultus (hiccup) treatment: three case reports. 1736 Jan 49

Proton pumps like the vacuolar-type H+ ATPase (V-ATPase) are involved in the control of cellular pH in normal and tumor cells. Treatment with proton pump inhibitors (PPI) induces sensitization of cancer cells to chemotherapeutics via modifications of cellular pH gradients. It is also known that low pH is the most suitable condition for a full PPI activation. Here, we tested whether PPI treatment in unbuffered culture conditions could affect survival and proliferation of human B-cell tumors. First, we showed that PPI treatment increased the sensitivity to vinblastine of a pre-B acute lymphoblastic leukemia (ALL) cell line. PPI, per se, induced a dose-dependent inhibition of proliferation of tumor B cells, which was associated with a dose- and time-dependent apoptotic-like cytotoxicity in B-cell lines and leukemic cells from patients with pre-B ALL. The effect of PPI was mediated by a very early production of reactive oxygen species (ROS), that preceded alkalinization of lysosomal pH, lysosomal membrane permeabilization, and cytosol acidification, suggesting an early destabilization of the acidic vesicular compartment. Lysosomal alterations were followed by mitochondrial membrane depolarization, release of cytochrome c, chromatin condensation, and caspase activation. However, inhibition of caspase activity did not affect PPI-induced cell death, whereas specific inhibition of ROS by an antioxidant (N-acetylcysteine) significantly delayed cell death and protected both lysosomal and mitochondrial membranes. The proapoptotic activity of PPI was consistent with a clear inhibition of tumor growth following PPI treatment of B-cell lymphoma in severe combined immunodeficient mice. This study further supports the importance of acidity and pH gradients in tumor cell homeostasis and suggests new therapeutic approaches for human B-cell tumors based on PPI.
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PMID:Proton pump inhibitors induce apoptosis of human B-cell tumors through a caspase-independent mechanism involving reactive oxygen species. 1754 22

Proton pump inhibitors have been used for treatment of acid-related gastroesophageal diseases and they act as potent inhibitors of gastric acid pump, H(+)/K(+)-ATPase. Since cancer cells in vivo often exist in an ischemic microenvironment with a lower pH, maintenance of cellular pH is important for cell survival. In this study, we evaluated whether blocking of proton extrusion with proton pump inhibitors could inhibit the viability of gastric cancer cells. Treatment of human gastric cancer cells with proton pump inhibitors significantly attenuated cell viability in a time- and dose-dependent manner. The pro-apoptotic activity of proton pump inhibitors was mediated by release of cytochrome c and caspases activation. Gastric cancer cells showed the resistance to acidity of culture medium, which was related with a remarkable increase of extracellular signal-regulated protein kinase 1/2 (ERK1/2) phosphorylation in the acidic condition. This ERK1/2 phosphorylation was completely inhibited by pretreatment with proton pump inhibitors, suggesting that its inhibitory action on phosphorylation of ERK1/2 might contribute to the induction of apoptosis in gastric cancer cells. In conclusion, our results suggest novel therapeutic approaches for gastric cancer with proton pump inhibitors.
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PMID:Blockage of intracellular proton extrusion with proton extrusions with proton pump inhibitor induces apoptosis in gastric cancer. 1795 91

Impedance monitoring is a new technique that can be used to detect the flow of fluids and gas through hollow viscera. With impedance monitoring gastro-oesophageal reflux can be detected independent of its acidity by differences in electrical impedance between the mucosal surface, fluids and gas that surround the catheter. Clinically, it is used in combination with oesophageal pH monitoring, and the combination of impedance-pH monitoring allows recognition of both acidic and weakly acidic reflux episodes. Studies have shown that impedance-pH monitoring is useful in the evaluation of patients with proton pump inhibitor-resistant typical reflux symptoms, as it provides a higher yield in detecting reflux as the cause of a patient's symptoms compared to pH monitoring alone. It is therefore likely that impedance-pH monitoring will largely replace pH monitoring in the next 5 years and it will become the standard for reflux detection.
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PMID:Impedance-pH monitoring: new standard for measuring gastro-oesophageal reflux. 1841

Using a previously described approach to generating novel medical hypotheses, this paper shows how two separate medical literatures taken together can suggest new information not apparent in either literature alone. Many studies have demonstrated that aerobic exercise in healthy people can induce esophageal acidic reflux that increases with the duration and intensity of exercise. Separately, independently of exercise, it has been shown that, in patients with gastroesophageal reflux, esophageal acid exposure can lead to atrial fibrillation (AF) and to other heart dysrhythmias. The two arguments together suggest that a regimen of excessive exercise may be conducive to AF mediated by acid reflux, an implicit, but unpublished, hypothesis. Proton pump inhibitors are widely used to treat gastroesophageal reflux. Remarkably, several small clinical trials of these drugs have been shown also to reduce symptoms and frequency of AF episodes in patients with comorbid acid reflux. Plausible mechanisms have been suggested. These small-scale tests in a highly restricted population may be of particular interest in the light of a possible exercise-reflux-AF causal chain of events in a broader population of athletes. Because the minimum degree of esophageal acidity exposure required to induce AF is unknown, further tests of proton pump inhibitors for that purpose are therefore merited without regard to any known prior reflux in a population of runners with lone AF. The prospect of reducing AF burden with a relatively benign agent is attractive in view of the limited options for effective treatment otherwise available. The study of arrhythmia and esophageal reflux in athletes may offer insights on the origin and natural history of lone atrial fibrillation.
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PMID:Running, esophageal acid reflux, and atrial fibrillation: a chain of events linked by evidence from separate medical literatures. 1845 18


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