Total Acid Secretion Research Articles

A novel gut inflammatory rat model by laparotomic injection of peptidoglycan from Staphylococcus aureus.

Inflammatory bowel disease includes ulcerative colitis and Crohn's disease, and is globally increasing. An appropriate model system is required to dissect the disease pathogenesis and drugs screening for adequate treatment. In the present study, we established a novel model of gut inflammation by injecting peptidoglycan from Staphylococcus aureus using laparotomic procedure. For this, three different doses of peptidoglycan, i.e., 2.5, 5 and 10mg/kg body weight were used. The treatment effect was evaluated by studying the macrophage phagocytic function, spleen lymphocytes' proliferation and qRT-PCR for the assessment of peritoneal cells' gene expression. In addition, histological analysis of gut sections, gastric acidity, immunoglobulins and cytokines were assessed. There was significant increase in phagocytic activity in 10mg/kg body weight PGN group. A dose dependent increase in spleen lymphocytes' proliferation and a significant increase in total acid secretion in 5 and 10mg/kg body weight PGN treated rats were observed. In addition, a significant increment in TLR-2 and CD-14 mRNA expression in peritoneal cells, TNF-α, IL-6 and IFN-γ level and maximum distortion of gut architecture was observed in 10mg/kg body weight PGN group. Hence, peptidoglycan from S. aureus can be used for establishing the screening model to study the action and mechanism of anti-inflammatory food products and drugs.

Comparative Study of Methanolic Extract of Banana, Ranitidine and Omeprazole on Total Acid Secretion and Gastric Ulcer Healing Effect in Albino Rats

Comparative Study of Methanolic Extract of Banana, Ranitidine and Omeprazole on Total Acid Secretion and Gastric Ulcer Healing Effect in Albino Rats

Oxyresveratrol ameliorates ethanol-induced gastric ulcer via downregulation of IL-6, TNF-α, NF-ĸB, and COX-2 levels, and upregulation of TFF-2 levels

Oxyresveratrol, an active ingredient of Artocarpus lakoocha, is known to possess anti-inflammatory and immunomodulatory properties. Current study investigates the immunomodulatory effect of oxyresveratrol in mouse model of ethanol-induced ulcer. Anti-ulcer effect was determined using histopathological evaluation (H&E staining) and different tests like, gastric ulcer scoring, ulcer index, total acid secretion, and gastric pH. The mRNA expression levels of interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), nuclear factor-kappaB (NF-ĸB), cyclooxygenase-1 (COX-1), cyclooxygenase-2 (COX-2) and trefoil factor 2 (TFF-2) were evaluated using reverse transcription polymerase chain reaction (RT-PCR). The data showed marked percentage inhibition of erosion, hemorrhage, fibrinoid necrosis, inflammatory infiltrate, and ulcer in low (30 mg/kg b.w.) and high dose (50 mg/kg b.w.) groups of oxyresveratrol. Treatment with oxyresveratrol inhibited ulcer score and ulcer index as compared with disease control group. Oxyresveratrol significantly increased gastric pH (P < 0.001) and attenuated total acid (P < 0.001) secretion. RT-PCR analysis showed significant suppression in the mRNA expression levels of IL-6 (P < 0.001), TNF-α (P < 0.01), NF-ĸB (P < 0.001), and COX-2 (P < 0.05) in oxyresveratrol treated groups, while COX-1 expression levels were found unaltered. Treatment with oxyresveratrol significantly elevated (P < 0.01) the expression levels of cytoprotective TFF-2 levels. Similar Immunomodulatory and anti-ulcer effects were found with ranitidine treatment, which was used as a reference drug. In conclusion, oxyresveratrol possess significant anti-ulcer property which might be attributed to attenuated expression levels of IL-6, TNF-α, NF-ĸB, and COX-2 and elevated expression levels of TFF-2.

The effects of baicalein on gastric mucosal ulcerations in mice: Protective pathways and anti-secretory mechanisms

Many flavonoids have been shown to present good results for the treatment of gastric ulcers. Baicalein, a bioactive flavonoid derived from the Scutellaria baicalensis Georgi root, possesses several biological effects, such as anti-inflammatory and antioxidant. This study was conducted to assess the gastroprotective properties of baicalein. Anti-ulcerogenic assay was performed using the protocol of ulcer induced by ethanol/HCl in mice; then, the role of presynaptic α2-receptors, sulfhydryl (SH) compounds, nitric oxide (NO), prostaglandin (PG) and ATP-sensitive K+ (KATP) channels in gastroprotection of baicalein was investigated. The levels of reduced glutathione (GSH) and the myeloperoxidase (MPO) activity were measured in the gastric mucosa. Parameters of gastric secretion (volume, [H+] and pH) were determined with or without the presence of the secretagogue agent histamine, as well as mucus in gastric contents, by the pylorus ligation model. In vitro H+,K+-ATPase activity was also determined. Baicalein (10, 30 and 100 mg/kg) exhibited a dose related gastroprotective effect (P < 0.001) against acidified ethanol-induced lesions. The intraperitoneal treatment of mice with a α2-adrenoreceptor antagonist (yohimbine; 2 mg/kg), a SH compounds blocker (N-ethylmaleimide, NEM; 10 mg/kg), a non-selective inhibitor of NO synthase (Nw-nitro-L-arginine methyl ester hydrochloride, L-NAME; 10 mg/kg), a non-selective inhibitor of cyclo-oxygenase (indomethacin; 10 mg/kg) or a KATP channel blocker (glibenclamide; 10 mg/kg) was able to reverse (P < 0.001) the gastroprotective response caused by baicalein (30 mg/kg). Baicalein (30 mg/kg; P < 0.05) was able to increase GSH levels and decreasing MPO activity. The intraduodenal treatment with baicalein (30 and 100 mg/kg) significantly increased (P < 0.05) the gastric mucus secretion. Additionally, the treatment with baicalein reduced (30 and 100 mg/kg; P < 0.05) the secretion volume and total acid secretion, and also increased (10, 30 and 100 mg/kg; P < 0.001) the pH value, after pylorus ligature. Baicalein (30 mg/kg) was also effective in inhibiting the effects of histamine on gastric secretion (volume, [H+] and pH; P < 0.001). Baicalein at 10 and 30 μg/mL showed anti-H+,K+-ATPase activity. In conclusion, the present results provide convincing evidence that baicalein could be used as a cytoprotective (preventive effect) and anti-ulcerogenic (anti-secretory effect) agent in the gastric ulcers.

Simultaneous detection of gastric acid and histamine release to unravel the regulation of acid secretion from the guinea pig stomach

Gastric acid secretion is regulated by three primary components that activate the parietal cell: histamine, gastrin, and acetylcholine (ACh). Although much is known about these regulatory components individually, little is known on the interplay of these multiple activators and the degree of regulation they pose on the gastric acid secretion mechanism. We utilized a novel dual-sensing approach, where an iridium oxide sensor was used to monitor pH and a boron-doped diamond electrode was used for the detection of histamine from in vitro guinea pig stomach mucosal sections. Under basal conditions, gastrin was shown to be the main regulatory component of the total acid secretion and directly activated the parietal cell rather than by mediating gastric acid secretion through the release of histamine from the enterochromaffin-like cell, although both pathways were active. Under stimulated conditions with ACh, the gastrin and histamine components of the total acid secretion were not altered compared with levels observed under basal conditions, suggestive that ACh had no direct effect on the enterochromaffin-like cell and G cell. These data identify a new unique approach to investigate the regulation pathways active during acid secretion and the degree that they are utilized to drive total gastric acid secretion. The findings of this study will enhance our understanding on how these signaling mechanisms vary under pathophysiology or therapeutic management.

Regulation of gastric acid secretion by gastrin in duodenal ulcer patients and healthy subjects

To examine the role of gastrin as a major mediator of meal-stimulated acid secretion at low and high intragastric pH, gastric acid secretory responses after exogenous and endogenous stimulation were studied in relation to circulating plasma gastrin levels in 19 healthy control subjects and in 18 patients with inactive duodenal ulcer disease. Gastrin was given intravenously in stepwise fourfold-increasing doses from 3.1 to 800 pmol · kg−1 · h−1 over consecutive 30-minute periods. Circulating plasma gastrin and acid secretion rates, measured by intragastric titration, were compared with the values obtained during endogenous stimulation by intragastric meals of 0.5, 1, 2, 4, and 8 g% peptone at either pH 5.5 or pH 2.5. The studies showed that circulating gastrin is a major regulator of acid secretion in the presence of peptone in both healthy controls and subjects with duodenal ulcers. Patients with duodenal ulcers had higher acid secretion rates in response to endogenous and exogenous stimulation. In duodenal ulcer subjects and healthy controls, acid secretion in response to higher doses (2–8 g%) of peptone was inhibited at low intragastric pH. This pH inhibition could be fully explained by diminished gastrin release. Patients in the DU group differed from the controls by diminished inhibition of acid secretion at intragastric pH 2.5 when low doses (1 g%) of peptone meals were used. In summary, gastrin is a major regulator of endogenously stimulated acid secretion at high and low intragastric pH in healthy subjects. DU patients differ from healthy controls by higher total acid secretion rates and diminished inhibition of acid secretion when low concentrations of peptone are present in the stomach.

Regulation of gastric acid secretion by gastrin in duodenal ulcer patients and healthy subjects

To examine the role of gastrin as a major mediator of meal-stimulated acid secretion at low and high intragastric pH, gastric acid secretory responses after exogenous and endogenous stimulation were studied in relation to circulating plasma gastrin levels in 19 healthy control subjects and in 18 patients with inactive duodenal ulcer disease. Gastrin was given intravenously in stepwise fourfold-increasing doses from 3.1 to 800 pmol.kg-1.h-1 over consecutive 30-minute periods. Circulating plasma gastrin and acid secretion rates, measured by intragastric titration, were compared with the values obtained during endogenous stimulation by intragastric meals of 0.5, 1, 2, 4, and 8 g% peptone at either pH 5.5 or pH 2.5. The studies showed that circulating gastrin is a major regulator of acid secretion in the presence of peptone in both healthy controls and subjects with duodenal ulcers. Patients with duodenal ulcers had higher acid secretion rates in response to endogenous and exogenous stimulation. In duodenal ulcer subjects and healthy controls, acid secretion in response to higher doses (2-8 g%) of peptone was inhibited at low intragastric pH. This pH inhibition could be fully explained by diminished gastrin release. Patients in the DU group differed from the controls by diminished inhibition of acid secretion at intragastric pH 2.5 when low doses (1 g%) of peptone meals were used. In summary, gastrin is a major regulator of endogenously stimulated acid secretion at high and low intragastric pH in healthy subjects. DU patients differ from healthy controls by higher total acid secretion rates and diminished inhibition of acid secretion when low concentrations of peptone are present in the stomach. (Gastroenterology 1992 Apr;102(4 Pt 1):1142-8)

The water extract of Coleus barbatus Benth decreases gastric secretion in rats

Coleus barbatus (Labiatae) Benth is popularly used in Brazil "for the healing of liver and stomach diseases". The water extract (WE 1 to 10 g/kg, p.o.) of stem and leaves given to rats and mice did not induce signs of intoxication. Previous treatment of mice with WE (1 g/kg, p.o.) shortened the sleeping time induced by pentobarbital (50 mg/kg, i.p.) by 37%, although the extract alone did not increase the spontaneous activity nor did it induce hyperexcitability. In mice WE (2 g/kg, p.o.) increased the intestinal transit of charcoal by 30%, while reduced gastric secretions in rats treated with WE (2 g/kg intraduodenal) (3.9 +/- 1.0 to 0.5 +/- 0.2 ml/4 h, respectively). The treatment also reduced the total acid secretion from 34.4 +/- 11.0 to 2.7 +/- 0.5 mEq/l and raised gastric pH from 2.2 +/- 0.3 to 6.5 +/- 0.8. Treatment with WE (2 g/kg, p.o.) protected against gastric ulcers induced by stress (5.3 +/- 1.6 and 1.5 +/- 0.5 ulcers/cm2), but it did not protect against indomethacin induced ulcers. The results show that the water extract of C. barbatus Benth produces mild stimulation of the central nervous system and increases intestinal movements. The extract also reduces gastric secretion indicating an antidyspeptic activity, and protects against gastric ulcers induced by stress.

Apical acidification by rabbit papillary surface epithelium

The rabbit papillary surface epithelium (PSE) is a simple cuboidal epithelium that covers the outer surface of the renal papilla and has an apical surface that faces the urinary space. We studied acid-base transport in this epithelium by dissecting it from the papilla, mounting it in a modified Ussing chamber, and following pH changes in the apical bathing solution. The experiments demonstrated that the PSE is capable of acidifying the apical solution at a substantial rate. The acidification rate was similar with 100% nitrogen and 100% oxygen (with and without 10 microM antimycin A), ruling out a dependence on oxidative metabolism. Addition of 1 mM iodoacetate decreased apical acidification by 55%, suggesting a dependence on glycolysis. The net rate of lactate secretion was only 17% of the total acid secretion rate, indicating that apical acidification was not directly caused by secretion of lactic acid alone. Removal of sodium or potassium from the apical solutions or the addition of 1 mM N-ethylmaleimide failed to eliminate the apical acidification. Although the rate of PSE apical acidification is comparable to that of the rabbit outer medullary collecting duct (on a unit surface area basis), its contribution to urinary net acid excretion is likely to be small, owing to the small relative surface area of the PSE. However, by altering the pH of urine locally within the pelvic recesses, the PSE has the potential of modifying the formation of renal stones within the pelvic recesses.

Gastric Aspiration Technique for pH Recording: A Critical Evaluation of This Method

The most often used methods for the measurement of intragastric acidity are repeated mostly hourly aspirations of gastric contents or continuous pH measuring with an electrode. Intragastric pH, volume of aspirated gastric juice and total acid secretion have been tested over relatively short periods of time (2-12 h) and through an entire 24-hour period. Nearly every clinical antiulcer drug which neutralizes acidity or inhibits acid secretion has been investigated with this method. pH monitoring with the gastric aspiration procedure is a reliable and reproducible method. There is a remarkable global agreement in the results. While pH electrodes provide an alternative means of measuring pH, they have the disadvantage of not allowing measurement of volume and/or acid secretion.

Invariant relation between total acid secretion and secretagogue exposure: secretory dynamics in bullfrog.

Using a continuous recording of acid secretion in frog gastric mucosa by pH-stat interfaced with a microcomputer, the pattern of secretion rate was studied under variable concentrations and durations of stimulation by histamine and forskolin. This tissue can respond with only a limited range of secretory rates. Larger concentrations and/or longer durations of stimulation may result in a secretion rate pattern prolonged far beyond the duration of stimulation. Although for the concentration-response curve the steady-state or peak acid secretion varies with the duration of stimulation, total acid secreted as a function of exposure to stimulator (time integral of the stimulatory pattern) is independent of the stimulatory pattern.

Urinary acidification in a patient with glucose-6-phosphate dehydrogenase deficiency: A reevaluation of the role of the hexose monophosphate shunt in renal acid secretion

The relationship between renal metabolism and urinary acidification is poorly understood. During the past decade evidence has accrued to suggest that the hexose monophosphate (HMP) shunt might serve in the process of urinary acidification by providing reducing equivalents for a redox-coupled membrane-bound proton pump that could transport protons into the tubular lumen. The major support for this hypothesis has come from the finding that HMP shunt activity increases with acute and chronic metabolic acidosis. In the present study, we examine the urinary acidification capacity of a young man with severe erythrocyte glucose-6-phosphate dehydrogenase (G-6-PD) deficiency and with unmeasurable G-6-PD activity in renal cortical tissue. We found that despite unmeasurable G-6-PD activity in renal tissue, the patient was capable of generating a maximally acid urine and increasing total acid secretion. Our findings suggest that the HMP shunt may not be necessary for the urinary acidification process.

Gastric Secretion and Motility After Vagotomy in Dogs

To study the changes in gastric secretion and motility after vagotomy, seven dogs were observed before and at intervals to one year after this operation. Methods: After thorough training and preoperative tests, seven mongrel dogs weighing from ten to eighteen pounds were sUbjected to transthoracic vagotomy. Three to five centimeters of the vagi were removed just above the diaphragm. One, three, six, nine and twelve months later tests were repeated. All studies were performed after a twenty-four hour fast. Gastric amilysis was performed after 1.0 mgm of histamine subcutaneously, after 2.0 mgm of urecholine subcutaneously and after 20 U of insulin intravenously. Titration was with 0.1 normal sodium hydroxide using Topfer's reagent and phenolphthalein as indicators. Gastric motility was recorded on a kymograph by a bromoform manometer connected to a Levine tube on the end of which was a rubber balloon. The 12tter was passed into the stomach and inflated with 250 cubic centimeters of air. Resting gastric motility and response to 2.0 mgm of urecholine subcutaneously and to 20 U of insulin intravenously were recorded. Emptying time was observed fluoroscopically after passage of 50 cubic centimeters of barium and water mixture into the stomach through a Levine tube. Results: The changes in free and total acid secretion are shown in figures 1, 2 and 3, and in the emptying time in table 1. By the method employed, the changes in intragastric pressure representing motility preoperatively showed waves from one to four centimeters of bromoform in height occurring at the rate of three to six per minute. After vagotomy, very small irregular waves were noted in most records, occasionally reaching the height of the preoperative test waves but infrequently attaining the same rate. In only nine of a total of sixty-three records were no waves seen. A few records showed large 8 to 20 centimeter waves, spaced at intervals of several minutes. Before and after operation, urecholine caused prompt increase in height and frequency of waves, with rapid increase in tone (height of lowest point of waves from base line). The maximum response was reached in from five to eight minutes. Occasionally the test was terminated at this point by the dog retching with breaking or expulsion of the balloon.