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Secretory and biosynthetic responses of gastrin and somatostatin to acute changes in gastric acidity.

The activity of gastric parietal cells in terms of hydrochloric acid (HCl) secretion is regulated by the interaction of stimulatory substances (e.g. gastrin) and inhibitors (e.g. somatostatin) acting in an endocrine and paracrine mode, as well as luminal factors. In the present study the following parameters were measured: the synthesis (mRNA), storage (tissue peptide concentration) and secretion (plasma peptide concentration) of somatostatin and gastrin following short-term treatment of rats with pentagastrin (acid stimulant), secretin, omeprazole (reduces gastric acidity by inactivating gastric H/K ATPase) and the somatostatin analogue octreotide (reduces gastric acidity by inhibiting both the parietal cell and gastrin). The mRNA coding for H/K ATPase and carbonic anhydrase II (CA II), the two enzymes responsible for the generation of hydrogen ions from the parietal cell, were also quantitated. In response to octreotide, somatostatin peptide and mRNA levels in the fundus rose to 180 +/- 16% (P < 0.001) and 1073 +/- 356% (P < 0.05) of control, respectively. In contrast, octreotide caused a decrease in antral somatostatin peptide and its mRNA did not change significantly. No significant changes in synthesis, secretion or storage of gastrin were observed except for omeprazole induced hypergastrinaemia (580 +/- 76%, P < 0.001). H/K ATPase and CA II mRNA were largely unaffected except for an increase in CA II mRNA following octreotide and a decrease in H/K ATPase mRNA after pentagastrin. These data support the concept of the differential control of antral and fundic somatostatin synthesis and provide evidence for a regulatory loop by which somatostatin can influence its own synthesis.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenosine Triphosphatases↗

[Bactericidal effect of acidic electrolyzed water--comparison of chemical acidic sodium hydrochloride (NaOCl) solution].

Acidic electrolyzed water is made recently by various kinds of machines and is widely utilized. In this study, we intended to clarify the relationship between the concentration of chloride and pH in the bactericidal effects with acidic electrolyzed water. The effects of weak or strong acidic electrolyzed water were compared with a pseudo-acidic water of pH adjusted by diluted hydrochloric acid and sodium hydroxide, on Staphylococcus aureus, Staphylococcus epidermidis and Pseudomononas aeruginosa. At pH 5.0 approximately 6.0, 3 bacterial strains were killed soon after being exposed to the acidic water containing chloride 50 mg/liter, and the amount of chloride did not change after allowing to stand open for 6 hours. At pH 2.67 approximately 2.80, the bactericidal effects was observed at the concentration of chloride 5 mg/liter, and 80% of chloride remained after allowing to stand for 6 hours. These results indicated that newly made strong acidic water is more effective under a smaller amount of chloride at pH 2.7, and that weak acidic electrolyzed water should be used, if stable bactericidal effect is expected in cleaning the surroundings.

Acids↗

Qualitative detection of muramic acid in normal mammalian tissues.

Rat tissues were extracted with 8% trichloroacetic acid, and the products were hydrolyzed with hydrochloric acid and purified. Fluorescamine derivatives were made and subjected to thin-layer chromatography; material with an Rf corresponding to the authentic muramyl derivative was obtained. It was oxidized with periodate, and the resulting formaldehyde was identified fluorimetrically. Alternatively, treatment with base released D-lactate (beta-elimination), which was identified fluorimetrically by reduction of NAD to NADH with D-lactate dehydrogenase. The data indicate that small muramyl compounds, presumably peptides of bacterial origin, are normally present in rat liver, brain, and kidney. The functions of muramyl compounds are suggested by much recent work.

Acetylmuramyl-Alanyl-Isoglutamine↗

pH effects on measurements of ionized calcium and ionized magnesium in blood.

CONTEXT: It is well known that the concentration of ionized calcium in blood is affected by the pH of the specimen, since hydrogen ions compete with calcium for binding sites on albumin and other proteins. However, the relationship between pH and ionized magnesium concentration is not as well characterized. OBJECTIVE: To determine the effects of pH on ionized magnesium concentration over a wide range of pH values in serum or plasma. DESIGN: Both ionized calcium and ionized magnesium concentrations were measured in 3 sets of samples. (1) Pools of serum or whole blood at different pH values (7.20-7.60) achieved by adding a constant volume of acid or base (diluted solutions of either hydrochloric acid or sodium hydroxide) plus saline. These pools consisted of 2 serum and 3 heparinized whole blood pools collected from leftover blood remaining in clinical specimens in the Clinical Chemistry and Blood Gas Laboratories, respectively, at Duke University Medical Center. (2) Five whole blood specimens obtained from apparently healthy individual donors. (3) Twenty-six whole blood specimens obtained from individual patients (leftover blood from the Blood Gas Laboratory) in which pH was varied by in vitro loss or gain of carbon dioxide. RESULTS: Both ionized calcium and ionized magnesium concentrations decreased as the pH in the specimen increased, indicating the stronger binding of these ions with proteins in the more alkaline environment. CONCLUSION: We conclude that the rate of change of ionized magnesium concentration with pH change (0.12 mmol/L per pH unit) is significantly less than that of ionized calcium (0.36 mmol/L per pH unit). Furthermore, our findings indicate that if adjustment to pH 7.40 is necessary, the ionized magnesium test results need to be adjusted when pH is markedly abnormal, as is sometimes done for ionized calcium.

Calcium↗

Cell physiology and pharmacology of gastric acid secretion.

Our stomach produces daily a large amount of hydrochloric acid at a pH close to 1. This secretion represents a more than one million-fold in H+ ion concentration as compared to blood and intracellular medium of a pH of 7.4. It is due to a specialized cell, the parietal cell, which contains a unique transport enzyme, the (H+, K+)-ATPase. The parietal cell is itself under the control of several endocrine and paracrine stimuli operating through appropriate receptors. The recent progresses achieved in the knowledge of these key elements of the acid secretion mechanism had led to the development of specific and potent inhibitors of crucial interest in the treatment of ulcer disease and reflux oesophagitis such as histamine H2 and (H+, K+)-ATPase antagonists.

Gastric Acid↗

[Experimental study of bacterial adherence to biliary tract in rabbits].

UNLABELLED: Adherence to host tissues and cell surfaces is an early step in infections. However nothing has been reported about bacterial adherence in biliary infections. The following experiment was carried out in rabbits with Escherichia coli isolated from the bile of a patient with acute suppurative cholangitis. Adhesion was observed by scanning electron microscopy. First, with cholecystic mucosa of normal, jaundice, acid (mucosa was injured with 0.1 N hydrochloric acid) and stone groups (stones were inserted into the gallbladder), bacterial adhesion as a virulence factor was examined in vitro. Second, in a cholangitis model the role of bacterial adherence to the bile duct in the development of localized biliary infection was examined in vivo. RESULT: (1) As compared to the normal, jaundice and stone groups, the number of adhering bacteria was remarkably increased in the acid group. The mucosa of the former groups was relatively intact, but that of the latter was remarkably destroyed. (2) In the cholangitis model, the number of bacteria adhered to the bile duct was negatively correlated with that of bacteria isolated from blood. These results suggest that bacterial adherence to the biliary tract is an important virulence factor, but not in the development from localized cholangitis to sepsis.

Animals↗

Comparative effect of cimetidine and gefarnate on normal and ulcerated albino rats.

Antiulcerogenic efficacies of cimetidine and gefarnate were compared in the normal, aspirin, acetic acid and stress induced ulcerated albino rats. In addition, their effects on output of gastric acid, pepsin and hexosamine were studied in normal and experimentally ulcerated rats. Gefarnate increased the glucosamine. levels in normal and ulcerated rats A significant reduction in ulcer formation was observed with gefarnate in aspirin, acetic acid and stress induced ulcerous rats. Cimetidine did not reduce acid output in the presence of exogenous hydrochloric acid in aspirin treated rats. A decrease in glucosamine concentration was also observed with cimetidine in aspirin treated rats. Thus cimetidine did not significantly reduced ulcer formation in ulcerated rats. In the present study, gefarnate was found to be more effective than cimetidine because of its effect in normalization of mucus barrier.

Journal Article↗

Development of a high-performance liquid chromatographic-post-column fluorogenic assay for digoxin in serum.

A quantitative, sensitive and specific assay for digoxin was developed using a high-performance liquid chromatographic (HPLC) system with post-column (PC) fluorogenic derivatization. Separation of digoxin from its metabolites was accomplished using a 15 cm X 4.6 mm I.D., 3-microns octadecylsilyl HPLC column and an optimum mobile phase of methanol-ethanol-isopropanol-dehydroascorbic acid (52:3:1:45, v/v). Concentrated hydrochloric acid, used as the PC derivatization reagent, was delivered by hexane displacement from a polyvinyl chloride pressure vessel. Construction of the pressure vessel is described. The mixture of HPLC effluent and PC reagent was passed into a 20-m knitted reactor (PTFE tubing) maintained at 79.0 +/- 0.2 degrees C. The resultant fluorophores were monitored by a fluorescence detector equipped with a 360-nm excitation filter and a 425-nm emission filter. Specificity of this HPLC-PC assay for digoxin in the presence of its metabolites was demonstrated. Also, numerous steroids evaluated did not produce fluorescence under these conditions. An extraction procedure for evaluating digoxin in serum without interference from endogenous compounds was also developed. Detector response to digoxin was linear from 0.5 to 3.3 ng extracted from serum.

Chromatography, High Pressure Liquid↗

Quantitative studies on acid hydrolysis of digitoxin.

Hydrolysis of 3H(G)-digitoxin by hydrochloric acid and human gastric juice is described. Incubation temperatures of 37 degrees C and 22 degrees C were chosen for electrolyte solutions, and 37 degrees C for the experiments with gastric juice. After dichloromethane extraction, the radioactive metabolites were separated by thin-layer chromatography, localized and quantified by a radiochromatogram scanner. The degradation products separated by TLC were digitoxigeninbis-digitoxoside, digitoxigenin-mono-digitoxoside, and digitoxigenin. After 10 min of incubation at pH 1, digitoxin amounted to 38.6% of the total radioactivity in electrolyte solution and 37.6% in gastric juice. After 60 min, the percentage of digitoxin decreased to 5.9% and 0%, respectively. After 120 min at 22 degrees C, amounts of unhydrolyzed digitoxin were: at pH 1 55%; and at pH 2 84%. After 10 min at pH 1, and 60 min at pH 2, digitoxin was hydrolyzed to such an extent that bioavailability should have been significantly reduced. Absorption of digitoxin (liquid) from the stomach was studied during gastroscopy in five patients. Among them, significant differences in absorption kinetics and bioavailability existed, as revealed by radioimmunological measurements of the digitoxin blood levels.

Chemical Phenomena↗

Gastric acid hypersecretion in children with duodenal ulcer.

Rates of gastric hydrochloric acid secretion were compared in 10 children with active duodenal ulcer (DU) and 14 non-duodenal ulcer children. Duodenal ulcer was diagnosed by gastroduodenoscopy or by evidence of an ulcer crater on upper gastrointestinal radiographs. Duodenal ulcer disease was excluded in the comparison group by similar criteria. Basal acid output in DU children tended to be higher, but the difference was not statistically significant (P greater than 0.05). Maximal acid output was significantly higher in DU children than in the comparison group whether expressed as milliequivalents per hour (P less than 0.025) or as milliequivalents per kilogram per hour (P less than 0.005). Peak acid output also showed a statistically significant difference (milliequivalents per hour, milliequivalents per kilogram per hour, (P less than 0.05). These findings demonstrate that, on the average, hypersecretion of gastric acid does occur in children with duodenal ulcer disease.

Adolescent↗

Gastroesophageal reflux-induced bronchoconstriction. An intraesophageal acid infusion study using state-of-the-art technology.

STUDY OBJECTIVE: To study mechanisms of gastroesophageal reflux-induced bronchoconstriction during intraesophageal infusions. DESIGN: Prospective study blinded to the subject. SETTING: Outpatient pulmonary function laboratory at a 908-bed university hospital. PARTICIPANTS: Forty-seven adult subjects divided into four groups: asthmatics with reflux, 20; asthmatics, 7; gastroesophageal refluxers, 10; and normal controls, 10. Asthmatics were defined by American Thoracic Society criteria, and refluxers were defined by symptoms and 24-hour pH monitoring. INTERVENTIONS: Dual antimony esophageal pH probe placed just below the upper esophageal sphincter and 5 cm above the lower esophageal sphincter. Intraesophageal infusions of normal saline solution followed by 0.1N hydrochloric acid then normal saline solution were given for 15 to 18 min. Spirometry and specific airway resistance (SRaw) were performed after placement of pH probes, insertion of esophageal infusion tube, and after each infusion. Bernstein tests were assessed during esophageal infusions. MEASUREMENTS AND RESULTS: Peak expiratory flow rate (PEF) decreased with intraesophageal acid in all four groups (p < 0.014). Esophageal acid clearance improved PEF in all groups except the asthmatics with reflux group that had a further decrease in PEF. These effects were not dependent on a positive Bernstein test or evidence of proximal reflux. The asthmatics with reflux group also had an increase in SRaw with intraesophageal acid, which continued to increase despite acid clearance. CONCLUSIONS: Intraesophageal acid infusions caused a decrease in PEF in all groups without evidence of microaspiration, implying a vagally mediated reflex may be involved. Esophageal mucosal inflammation, assessed by a positive Bernstein test, was not required. Asthmatics with reflux also had further decline in PEF despite acid clearance.

Adult↗

Trace elements in rock salt and their bioavailability estimated from solubility in acid.

In this study, 18 partly commercially available samples of rock salt from Austria, Germany, Pakistan, Poland, Switzerland, and Ukraine were investigated with respect to their content of trace elements using instrumental neutron activation analysis. Elements detected were Al, Ba, Br, Ca, Ce, Cl, Co, Cr, Cs, Eu, Fe, Hf, La, Mn, Na, Rb, Sb, Sc, Sm, Sr, Ta, Tb, Th, and Zn, some of them only in individual cases. An estimation of the bioavailability of these trace elements was performed by dissolving an equivalent of the sodium chloride samples in diluted hydrochloric acid (simulating stomach acid), filtering off the insoluble components, and analyzing the evaporated filtrate. It could be shown that in most cases bioactive trace elements like Fe can be found in rock salt in the form of almost insoluble compounds and are therefore not significantly bioavailable, whereas thorium, for example, was partly bioavailable in two cases. A significant contribution to the recommended daily intake of metal trace elements by using rock salt for nutrition can be excluded.

Biological Availability↗

Appearance of specific mucins recognized by monoclonal antibodies in rat gastric mucosa healing from HCl-induced gastric mucosal damage.

BACKGROUND: Mucus is an important factor in the physiological defense mechanism of the gastrointestinal tract. We have reported that two distinct antigenicities reacting with anti-mucin monoclonal antibodies (mAbs), HCM31 and RGM26, emerged in epithelial cells regenerating from acetic acid-induced gastric damage in the rat. Here, we examined whether the expression of specific mucins occurred during the healing stage of acute gastric mucosal lesions, and what was the principal alteration of the mucus in the regenerating process of gastric epithelia from slight mucosal lesions. METHODS: Eight-week-old male Wistar rats were used. The animals were administered 0.6 N hydrochloric acid, or 0.5% carboxymethyl cellulose sodium salt into their stomachs. Twenty-four, 48, and 72 h after the HCl administration, their stomachs were removed. Immunohistochemical observation was performed after staining with the mAbs, RGM21, RGM26, HIK1083, or HCM31. RESULTS: Twenty-four hours after the administration of HCl, mucous cells stained with RGM26 emerged in the deeper area of the surface epithelial cells in the damaged corpus mucosa. After 48 h, HCM31-positive cells were noted in the epithelial cells where the mucosal damage reached more deeply. CONCLUSIONS: The appearance of specific mucin species was observed in the regenerating epithelia of the rat during the healing process from acute gastric mucosal damage.

Animals↗

Necrotic skin lesion following therapy of severe metabolic alkalosis. A case report.

An outward side effect of HCl infusion during the treatment of severe metabolic alkalosis is reported. Solution of 0.2 n hydrochloric acid, infused via a peripheral vein caused necrotic lesions of skin and subcutaneous tissue. In case that the central parenteral route is precluded, oral therapy with diluted HCl solution may be considered.

Alkalosis↗

Acid-induced duodenal mucosal nitric oxide output parallels bicarbonate secretion in the anaesthetized pig.

We recently showed the involvement of the L-arginine/nitric oxide (NO) pathway in acid-induced duodenal mucosal bicarbonate secretion in rats. The aim of the present study was to confirm this observation in pigs by direct measurements of NO production. Experiments were performed on 16 anaesthetized pigs of both sexes treated with guanethidine (6 mg kg-1, intravenously). A duodenal segment, devoid of pancreaticobiliary influxes, was perfused with saline and the duodenal mucosal bicarbonate secretion was calculated from continuous measurements of pH and PCO2. The perfusate contents of NO and its oxidative product nitrite were determined by chemiluminescence, after reduction of nitrite to NO. Luminal acidification with 30 mM hydrochloric acid increased the output of bicarbonate as well as NO to the perfusate, by 195 +/- 45% and 106 +/- 10%, respectively. These responses to acid were markedly inhibited by adding the NO synthase inhibitor NG-monomethyl-L-arginine (L-NMMA, 0.3 mM) to the perfusate. The inhibitory effect of L-NMMA could be reversed by administration of L-arginine (3 mM). The study presents simultaneous measurements of bicarbonate and NO outputs to a duodenal luminal perfusate. The results strongly support the view that the L-arginine/NO pathway is involved in the acid-induced duodenal mucosal bicarbonate secretory response.

Anesthetics, Combined↗

The effect of acidifying the duodenal contents on splanchnic blood flow.

Acidifying the duodenal contents with 0.1 N hydrochloric acid in the dog increased both hepatic artery and portal vein flow, and reduced mesenteric vascular resistance as well as hepatic artery and portal venous inflow resistances. The reaction is absent after intraduodenal injection of 30% glucose and physiological saline solutions. More concentrated acid leads to a greater increase in blood flow. The receptors of the circulatory reflex are situated in the duodenal mucosa and can be blocked with lidocaine.

Animals↗

Effects of esophageal acid perfusion on airway hyperresponsiveness in patients with bronchial asthma.

STUDY OBJECTIVES: The effects of gastroesophageal reflux on airway hyperresponsiveness in patients with bronchial asthma have yet to be studied in significant detail. The purpose of the present study was to determine how esophageal acid perfusion could change airway responsiveness in patients with bronchial asthma. PATIENTS AND INTERVENTIONS: In seven patients with bronchial asthma (mean +/- SD age, 55.1 +/- 6.4 years; four women and three men), esophageal pH was monitored by a pH meter and airway responsiveness was evaluated by aerosol inhalation of methacholine, during esophageal perfusion through an esophageal tube filled with either saline solution or 0. 1N hydrochloric acid (HCl), the order of which was selected at random, in 1-week intervals. Spirometry was also performed during esophageal pH monitoring. RESULTS: A significant decrease in the geometric mean of airway sensitivity or the concentration of methacholine causing a 35% fall in respiratory conductance was observed during esophageal HCl perfusion compared with that of saline solution perfusion (p < 0.01 or p < 0.003), although no significant changes were observed in vital capacity, FEV(1), peak expiratory flow, respiratory resistance, or slope of respiratory conductance during the periods of saline solution and HCl perfusion. CONCLUSION: We concluded that an increase in airway hyperresponsiveness was induced when HCl stimulated the esophagus in patients with bronchial asthma. These results suggest that esophageal reflux is one of the important factors that aggravate asthmatic status.

Adult↗