Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P00790 (PGA)
 2,475 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In a series of in vitro studies, both the soluble (plasmatic) coagulation system and the cellular (platelet-mediated) aspect of coagulation were shown to be extremely sensitive to relatively minor increases in hydrogen ion concentration. All studies became abnormal at pH 6.8. At pH 6.4, assays of the intrinsic and extrinsic coaglution systems, the polymerization of fibrinogen, and assay of the availability of platelet phospholipid (platelet factor 3) were twice prolonged over control values. Platelet aggregation was reduced by more than 50%. At pH 5.4 in vitro, platelet aggregation and plasma coagulation were both virtually abolished. Furthermore, previously formed platelet aggregates disaggregated at a slightly acid pH. Pepsin further enhanced platelet disaggregation. Because gastric acidity is normally two to four orders of magnitude greater than that which abolishes platelet aggregation and plasma clotting in vitro, and pepsin is present in abundance, we call attention to the probable antihemostatic effect of hydrocloric acid and pepsin in the upper gastrointestinal tract. This in vitro study may provide a rationale for meticulous regulation of intragastric pH in an effort to control upper gastrointestinal hemorrhage.
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PMID:Effect of acid and pepsin on blood coagulation and platelet aggregation. A possible contributor prolonged gastroduodenal mucosal hemorrhage. 2 30

Artificial clots made from fibrin glue with and without an inhibitor of fibrinolysis can be used to treat gastrointestinal bleeding. We have been unable to find descriptions of the effects of acid and pepsin upon such artificial clots. Therefore, 10(-2) mol/l epsilon aminocaproic acid was added to fibrin glue in vitro at acid concentrations of pH 1.0 and pH 5.5. Pepsin was added at 9000 U/50 ml, the expected value for fasting human subjects. There was a highly significant reduction in clot survival at pH 1.0. At pH 5.5, clot weight was also significantly decreased with pepsin, compared to control. Thus pepsin and acidity greatly affect survival of artificial clots, but the addition of epsilon aminocaproic acid did not affect clot survival.
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PMID:Pepsin fibrinolysis of artificial clots made from fibrinogen concentrate and bovine thrombin: the effect of pH and epsilon aminocaproic acid. 251 Mar 30

The gastric antisecretory effects of two dose levels of pirenzepine given at night were investigated in a group of healthy male volunteers. Compared with placebo, three days of treatment with pirenzepine 100 mg nocte or 150 mg nocte inhibited mean nocturnal intragastric acidity by 54% and 53%, respectively (p less than 0.01). The volume of gastric juice secreted was reduced by 47% and 52% (p less than 0.005), by 100 mg and 150 mg nocte, respectively. Each dose suppressed mean gastric acid output by 67% (p less than 0.001). Pepsin output was not significantly altered. There were no differences in effect between the two dose levels studied, but side-effects such as dry mouth were only seen with the higher dose. Pirenzepine 100 mg is the optimum dose which can conveniently be given at night. This will limit side-effects, and may be a useful treatment for patients with duodenal ulcer.
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PMID:Single nocturnal doses of pirenzepine effectively inhibit overnight gastric secretion. 286 23

In healthy human volunteers, a single oral dose of enprostil (35 micrograms) inhibited basal gastric acid output by a mean of 71 percent, pentagastrin-stimulated output by 46 percent, sham-meal-stimulated output by 48 percent, and histamine-stimulated output by 16 percent. In each case, there was a reduction in both the volume and acidity of the gastric juice. Pepsin output was unchanged. Although enprostil increased the gastric pH, it did not induce basal or post-prandial hypergastrinemia. In patients with hypergastrinemia secondary to achlorhydria, enprostil lowered the basal gastrin level and reduced or abolished the post-prandial gastrin rise in a dose-related fashion. Enprostil reduces basal and stimulated gastric acid secretion and inhibits gastrin release.
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PMID:Effect of a single oral dose of enprostil on gastric secretion and gastrin release. Studies in healthy volunteers and patients with pernicious anemia. 309 53

Duodenal ulcer therapy with H2 antagonists initially aimed to control acid secretion throughout the 24-h period, but recently nighttime suppression has been advocated. The effect of single nighttime regimens of cimetidine 400 mg BID, cimetidine 800 mg HS, ranitidine 150 mg HS, and placebo on 24-h intragastric acidity, nocturnal acid output, and pepsin secretion were studied in four healthy volunteers and four patients with healed duodenal ulcer. A nonrandomized dose of cimetidine 1200 mg HS was also studied. For all four treatments, daytime (0730-2230 h) intragastric acidity was reduced by 4-30% in the normals and by 10-44% in the duodenal ulcer patients (NS), while 24-h intragastric acidity was reduced by 44-46% and 40-64%, respectively (p less than 0.05). Reduction in nocturnal acid output was 82-96% in normals and 91-99% in duodenal ulcer, respectively. Pepsin concentration was unaffected by treatment but pepsin concentration was significantly (p less than 0.05) lower in patients than in normals. Mean 24-h gastric acid secretion was reduced by a single nighttime treatment with an H2-receptor antagonist, while nocturnal acid secretion was virtually abolished. H2 antagonists given only at night deserve further clinical evaluation to determine the minimal effective dose and optimal duration of suppression to achieve ulcer healing.
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PMID:A double-blind randomized study comparing different dose regimens of H2-receptor antagonists on 24-hour gastric secretion in normal subjects and duodenal ulcer patients. 309 64

Pepsin and its multiple molecular forms have been studied in pre-term and post-term Nigerian infants. The levels of total enzyme activity and acidity were lower in the pre-term infants when compared to term and post-term infants. Resolutions of the various species by ion-exchange chromatography and electrophoresis revealed that the development of specific isoenzymes in term infants occurred towards the end of the neonatal period. Differential development of the enzyme and the isoenzyme in the neonatal period may have important clinical bearing on the subsequent pancreatic protease hydrolysis which may provide a basis for evaluating gastric capacity for nutritional management of these infants.
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PMID:Pepsin and its multiple forms in early life. 313 54

Gastric secretion was measured in nine patients with duodenal ulcer before, and after treatment for four weeks with omeprazole 20 mg or 40 mg daily. Basal acidity and acid output were affected variably by 20 mg, but inhibited totally by 40 mg daily. Sham feed stimulated acid output was reduced by 20 mg daily and completely inhibited by 40 mg daily. Maximal pentagastrin stimulated acid output was halved by 20 mg omeprazole daily and 84% inhibited by 40 mg daily. The reduction in acidity was always greater than the reduction of volume. Pepsin output after pentagastrin was little altered but with the reduced secretory volume pepsin concentrations were increased by both doses. The major cause of reduced aspirate acid output after omeprazole is decreased secretion of the primary acid component of the parietal cell by the proton pump H+K+ ATPase. Duodenogastric alkaline reflux is, however, markedly increased after omeprazole and is an additional factor in the resultant hypoacidity or even anacidity after this drug.
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PMID:Basal, sham feed and pentagastrin stimulated gastric acid, pepsin and electrolytes after omeprazole 20 mg and 40 mg daily. 393 37

Pharmacological screening tests have been done in order to provide an initial assessment of the new antacid compound almagate (aluminium-magnesium hydroxycarbonate hydrate, Al2Mg6(OH)14(CO3)2 X 4 H2O, Almax). In rats with pyloric ligatures, almagate (125-500 mg/kg) was significantly more potent than aluminium hydroxide in raising the pH and reducing the total acidity of the gastric juice produced, without affecting the volume secreted. Pepsin activity in the gastric juice was also significantly inhibited by almagate even after adjustment to the optimal enzyme pH 2, a phenomenon not demonstrable with aluminium hydroxide. Almagate in oral doses up to 3 g/kg was without effects on the central, autonomic and somatic nervous systems in mice, nor at 500 mg/kg did it influence the cardiovascular system or blood pressure responses to agonist drugs in anaesthetised cats. The results confirm almagate to be a potent antacid drug devoid of systemic pharmacological or toxicological effects.
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PMID:Pharmacological studies with almagate, a potent new antacid compound. 654 22

Gastric fistula rats (n = 79) were either left as unstressed (fistula closed) controls or gastric secretion, microcirculation (MBF), mucosal stress ulcers were studied in secretory rats subjected to zero (= freely movements allowed), mild, severe restraint stress for 8 h. In all rats gastrin in portal vein and aorta was measured in addition after discontinuation of either protocol. Acid secretion and MBF are progressively reduced by increasing stress. Pepsin and sodium are elevated with severe, acid concentration with mild stress. Pepsin and sodium are elevated with severe, acid concentration with mild stress. Serum gastrin (controls - aorta 53+/- SEM 5, portal vein 73 +/- 9 pg/ml) rises sharply in portal and systemic blood with institution of acid diversion via the outside (zero stress - 136 +/- 21, 398 +/- 98 pg/ml), but declines with increasing stress (severe stress - 82 +/- 16, 101 +/- 27 pg/ml) despite otherwise identical experimental conditions. It is concluded that (1) acid secretion rate and MBF are lowered by stress, but stress ulcers are associated with either increased acidity (mild stress) or peptic activity (severe stress) of gastric juice in the absence of elevated gastrin, (2) enhanced sodium fluxes via gastric lumen and lower acid suggest disruption if mucosal barrier by severe stress, and (3) restraint stress ulcers may be the expression of a combination of disturbances, mainly of metabolic and endocrine nature.
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PMID:Gastric secretion, mucosal erosions and porto-systemic gastrin gradients as influenced by different degrees of stress in the rat. 732 53

Sialic acids occupy terminal positions on gastric mucus glycoprotein where they contribute to the high viscosity of mucin. Desialylation of mucus may lead to degradation of the mucus and eventually to the breakdown of the gastric mucus barrier. The effect of a variety of damaging agents (0.1 M HCl, 2 mg ml(-1) pepsin and 2 M NaCl) on sialic acid profile was determined in pylorus-ligated rats. The relationship between sialic acid, galactose, pyruvate and the extent of gastric mucosal damage were studied. Instillation of pepsin significantly increased total sialic acid, galactose and macroscopic mucosal lesions in the stomach. Instillation of 0.1 M HCl reduced the total sialic acid but this decrease was not significant. Acidity led to a significant increase in the amount of free sialic acid in the gastric instillates and the macroscopic lesions induced by acid was not significantly different from the control animals (0.15 M NaCl). 2 M NaCl induced the macroscopic lesions in the stomach and also free sialic acid in the instillates. Pepsin potentiates the action of 2 M NaCl. In all the agents examined with the exception of acid, it was observed that an increase in free sialic acid and galactose was accompanied by gastric mucosal erosion and elevation of pyruvate concentration. It is concluded that gastric acidity alone is not inherently damaging and that resistance of gastric mucosa to destructive agents may be dependent on the integrity of the sialic acids.
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PMID:Correlation of gastric mucosal damage with sialic acid profile in rats: effect of hydrochloric acid, pepsin and hypertonic saline. 1551 24


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