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)

Linolenic acid (C18:3) is the main endogenous unsaturated fatty acid of thylakoid membrane lipids, and seems in its free form to exert significant effects on the structure and function of photosynthetic membranes. In this investigation the effect of linolenic acid was studied at various pH values on the electron flow rate in isolated spinach chloroplasts and related to deltapH, the proton pump and the pH of the inner thylakoid space (pHi). The deltapH and pHi were estimated from the extent of the fluorescence quenching of 9-aminoacridine. Linolenic acid caused a shift (approximately one unit) of the pH optimum for electron flow toward acidity in the following systems: (a) photosystems II + I (from H2O to NADP+ or to 2,6-dichlorophenolindophenol) coupled or non-coupled; (b) photosystem II (from H2O to 2,6-dichlorophenolindophenol in the presence of dibromothymoquinone). In photosystem I conditions (phenazine methosulphate), the deltapH of the control increased as a function of external pHo with a maximum around pH 8.8. When linolenic acid was added, the deltapH dropped, but its optimum was shifted toward more acidic pHo. The same phenomena were also observed in photosytems II + I (from H2O to ferricyanide) and in photosystem II conditions (from H2O to ferricyanide in the presence of dibromothymoquinone). However, the deltapH was smaller and the sensitivity of the proton gradient toward linolenic acid was eventually higher than for photosystem I electron flow activity. The proton pump which might be considered as a measure of the internal buffering capacity of thylakoids was optimum at pHo, 6.7 in the controls. An addition of linolenic acid diminished the proton pump and shifted its optimum toward higher pHo. As a consequence, pHi increased when pHo was raised. At the optimal pHo 8.6 to 9, pHi were 5 to 5.5. Additions of increasing concentrations of linolenic acid displaced the curves toward higher pHi. A decrease of pHo was therefore required to maintain the pHi in the range of 5-5.5 for maximum electron flow. In conclusion, the electron flow activity seems to be delicately controlled by the proton pump (buffer capacity), deltapH, pHi and pHo. Fatty acids damage the membrane integrity in such a way that the subtile equilibrium between the factors is disturbed.
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PMID:Influence of unsaturated fatty acids in chloroplasts. Shift of the pH optimum of electron flow and relations to deltapH, thylakoid internal pH and proton uptake. 0 70

The role of gastric acid in the development of gastroduodenal ulcers in prostaglandin-deficient conditions is unclear. In the current study, the effect of the proton pump inhibitor omeprazole on the formation of gastric ulcers was examined in a previously validated rabbit model of antibody-induced prostaglandin deficiency. Intragastric administration of 20 mg/kg omeprazole every 12 hours caused a profound suppression of gastric acidity (i.e., pH above 5 continuously). This same dose of omeprazole significantly reduced gastric ulcer formation induced by passive immunization with 6-keto-prostaglandin F1 alpha antibodies. It is concluded from these observations that gastric acid plays a critical role in the formation of gastric ulcers in rabbits with antibody-induced prostaglandin deficiency.
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PMID:Importance of gastric acid in gastric ulcer formation in rabbits with antibody-induced prostaglandin deficiency. 142 65

Omeprazole blocks the final step of gastric acid secretion by blocking the proton pump (the hydrogen and potassium ATPase) in gastric parietal cells. Due to this direct action, omeprazole is the most potent, clinically available suppressor of gastric acidity.
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PMID:Omeprazole in the treatment of peptic ulcers and gastroesophageal reflux disease. 146 81

The regulation of gastric somatostatin is linked to changes in gastric acidity, with a number of studies showing a good correlation between somatostatin secretion and gastrin-stimulated luminal acidity. However, gastrin may also have direct effects on somatostatin secretion independent of the concurrent acid status. We have examined the relative contribution of gastrin itself vs. gastric acid on the increase in somatostatin secretion observed after gastrin administration. Pentagastrin administered to conscious sheep for 2 h caused a 10- to 12-fold increase in both portal venous and peripheral jugular venous plasma somatostatin levels. This was associated with a decrease in gastric pH from 3.5 to 1.7. When the sheep were pretreated with the proton pump inhibitor omeprazole to prevent any change in gastric acidity, pentagastrin caused a similar increase in plasma somatostatin. The increase in somatostatin could also be produced by gastrin-17 infusions. Thus, these studies demonstrate that in the conscious animal gastrin can stimulate somatostatin independent of changes in gastric acidity. It is proposed that there is a negative feedback between somatostatin and gastrin, which may modulate the acid secretory response to gastrin.
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PMID:Regulation of somatostatin secretion by gastrin- and acid-dependent mechanisms. 168 34

The development of effective antisecretory drugs has risen the question of what is the ideal inhibition of gastric acid secretion in the treatment of peptic ulcer. Cimetidine, unlike the more recent H2-blockers and proton pump inhibitors, exerts antisecretory effects that are correlated to the blood levels of the drug. For this reason, therapeutic posologies were initially based on the pharmacokinetic features of the drug, while, more recently, direct measurement of intragastric acidity have assumed great relevance. Despite extensive research, the ideal level of gastric acid inhibition in the treatment of peptic ulcer has not been established. Greater healing rates are achieved by more potent antisecretory drugs and the duration of treatment appears to be also important, particularly to the healing of gastric ulcers. Whether the course of peptic ulcer disease is affected by the potency of the drug employed in the treatment of acute episodes has not been established.
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PMID:Inhibition of gastric acid secretion and therapeutic results: is there any correlation? 198 21

Omeprazole is a specific inhibitor of H+,K(+)-ATPase or 'proton pump' in parietal cells. This enzyme is responsible for the final step in the process of acid secretion; omeprazole blocks acid secretion in response to all stimuli. Single doses produce dose-dependent inhibition with increasing effect over the first few days, reaching a maximum after about 5 days. Doses of omeprazole 20mg daily or greater are able to virtually abolish intragastric acidity in most individuals, although lower doses have a much more variable effect. Omeprazole causes a dose-dependent increase in gastrin levels. Omeprazole must be protected from intragastric acid when given orally, and is therefore administered as encapsulated enteric-coated granules. Absorption can be erratic but is generally rapid, and initially the drug is widely distributed. It is highly protein-bound and extensively metabolised. Its elimination half-life is about 1h but its pharmacological effect lasts much longer, since it is preferentially concentrated in parietal cells where it forms a covalent linkage with H+,K(+)-ATPase, which it irreversibly inhibits. Omeprazole binds to hepatic cytochrome P450 and inhibits oxidative metabolism of some drugs, the most important being phenytoin. Omeprazole has produced short term healing rates superior to the histamine H2-receptor antagonists in duodenal ulcer, gastric ulcer and reflux oesophagitis. It has also been shown to be highly effective in healing ulcers which have failed to respond to H2-receptor antagonists, and has been extremely valuable in treating patients with Zollinger-Ellison syndrome.
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PMID:Clinical pharmacology of omeprazole. 202 1

Omeprazole represents the first agent of a unique class of acid inhibitory drugs, the proton pump inhibitors. Omeprazole inhibits basal gastric acid secretion, as well as gastrin-, histamine-, or pentagastrin-stimulated secretion, which results in decreased gastric acidity, decreased gastric acid output, and decreased gastric volume. Omeprazole is acid labile, necessitating its oral administration in an enteric-coated formulation. Bioavailability appears to be dose-dependent, with more drug being absorbed with increasing dosage as well as after repeated dosing. This is probably secondary to decreased gastric acidity and, therefore, less degradation of the administered drug. Despite its relatively short half-life (1-2 h), omeprazole's pharmacologic action is prolonged. Clinical trials have shown omeprazole to be at least as effective as histamine2-receptor antagonists in the treatment of gastric ulcers, duodenal ulcers, gastroesophageal reflux, and Zollinger-Ellison syndrome. Adverse reactions have been minimal. Omeprazole has been approved by the Food and Drug Administration for short-term therapy of severe erosive esophagitis, poorly responsive symptomatic gastroesophageal reflux disease, and long-term management of Zollinger-Ellison syndrome.
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PMID:Omeprazole: a novel antisecretory agent for the treatment of acid-peptic disorders. 218 94

Medical management of peptic ulcer disease continues to evolve with the recent introduction of new H2-receptor antagonists, prostaglandin analogs, and a proton pump inhibitor, and clarification of the relationship between suppression of gastric acidity and ulcer healing. Nizatidine and roxatidine acetate, the new H2 blockers, are safe and effective but do not appear to have new properties of clinical importance. The modes of action of omeprazole and the prostaglandins have been clarified. Omeprazole is a prodrug that is protonated and secured in the secretary canaliculus of the parietal cell where the active derivative covalently binds sulfhydryl groups of H+/K(+)-ATPase, thereby irreversibly and profoundly blocking acid secretion. Prostaglandins bind a receptor on the basolateral membrane of the parietal cell, releasing a protein that inhibits cyclic AMP, the second messenger of histamine-stimulated acid secretion. The ulcer-healing properties of prostaglandins can be attributed largely if not entirely to their inhibition of acid secretion. Antacids, on the other hand, may heal ulcers by effects other than acid neutralization, as the low-dose regimens that heal ulcers only weakly neutralize acid. The way in which sucralfate and colloidal bismuth heal ulcers remains unclear; they may do so through multiple effects including, in the case of bismuth, eradication of C. pylori. H2-receptor antagonists continue as first-line treatment for acute DU and GU and the prevention of recurrence. The antacid and sucralfate regimens are less convenient but safe and effective. Misoprostol has a disadvantageous safety profile relative to available agents but is effective in preventing NSAID-induced gastric ulcers. The efficacy of omeprazole in acid-peptic disease is established but the way in which it should be used is still unclear because of long-term safety concerns.
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PMID:Overview of medical therapy of peptic ulcer disease. 218 24

1. Helicobacter pylori has been associated with chronic type-B gastritis, which in turn is always present in duodenal ulcer patients; therefore, it is likely that Helicobacter pylori is an important cofactor in the pathogenesis of peptic ulcer disease. An eradication of Helicobacter pylori is associated with the reduced ulcer relapse rate, but an effective therapy for eradication is not yet available and should be restricted to experimental protocols. 2. Omeprazole is an antagonist of the proton pump of the acid-producing cell of the human stomach. With once-daily omeprazole treatment it is possible to almost abolish 24-hour intragastric acidity in the majority of duodenal ulcer patients; therefore, omeprazole allows alternative treatment of different causes of peptic disease.
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PMID:[Current perspectives in ulcer disease]. 221 69

Intraluminal pH was measured simultaneously in the stomach and duodenal bulb with six small, glass electrodes tied together at 1.5-cm intervals. Ten patients with duodenal ulcer disease were studied under fasting conditions and for 3 h after a standard liquid meal on three occasions: day 1, before treatment; day 8, when the proton pump blocker omeprazole had been taken in a daily dose of 30 mg for 7 days consecutively, including the day of the pH study; day 9, 24 h after the last dose of omeprazole. Mean hydrogen ion activity and the percentage of time with pH below 3 was calculated from the digital pH data sampled at a frequency of 1 per second from each electrode. On day 8, five of the patients were permanently anacidic (pH greater than 4) in the stomach and duodenum, while the food-stimulation broke off anacidity for shorter periods in the other five patients. The pH pattern in the duodenal bulb was markedly altered in all patients with disappearance of the typical pH fluctuations, and a decrease in the time that the pH was below 3 from a median value of 30% before treatment to 0% in seven patients and close to 0% in three patients. On day 9, a large patient-to-patient variation was observed in gastric pH: three patients were still anacidic, four were markedly suppressed, but three patients reached near pre-treatment acidity. Duodenal bulb acidity was still decreased significantly on day 9 in all patients, with post-prandial pH below 3 for less than 5% of the time, compared with 30% before treatment.
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PMID:Effect of omeprazole on intragastric and duodenal bulb acidity in duodenal ulcer patients. 249 66


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