Adaptive cytoprotection by 0.25 M HCl is truly "cytoprotective" and may not depend upon elevated levels of prostaglandin synthesis

1988 ◽  
Vol 66 (8) ◽  
pp. 1075-1081 ◽  
Author(s):  
W. K. MacNaughton ◽  
T. E. Williamson ◽  
G. P. Morris
Keyword(s):  
Ex Vivo ◽  
Potential Difference ◽  
Surface Epithelium ◽  
Lesion Area ◽  
Damage Potential ◽  
Adaptive Cytoprotection ◽  
Epithelial Damage ◽  
Subsequent Exposure ◽  
Rat Gastric Mucosa ◽  
Mild Irritant

The ability of a mild irritant to reduce ethanol-induced damage to the rat gastric mucosa was investigated using an ex vivo gastric chamber preparation. Exposure to 0.25 M hydrochloric acid (HCl) did not cause significant damage to the surface epithelium, but did reduce both the lesion area and the extent of superficial epithelial damage caused by subsequent exposure to 40% ethanol (EtOH). "Adaptive cytoprotection" was also demonstrated by the reduction of ethanol-induced changes in transmural potential difference and net K+ efflux, and by rapid recovery of these physiological parameters following the removal of ethanol from the chamber. Pretreatment of rats with indomethacin at a dose that has been shown to significantly inhibit gastric cyclooxygenase activity did not significantly affect the ability of 0.25 M HCl to reduce the effects of ethanol on lesion area, epithelial damage, potential difference, and net K+ efflux.

scholarly journals The Effect of Cimetidine on Adaptive Cytoprotection by Mild Irritant Dose of HC1 in the Rat Gastric Mucosa

1991 ◽  
Vol 57 (1) ◽  
pp. 63-70 ◽  
Author(s):  
Shinichi Ota ◽  
Hideyuki Hiraishi ◽  
Akira Terano ◽  
Hiroyuki Mutoh ◽  
Yasuo Hata ◽  
...  
Keyword(s):  
Gastric Mucosa ◽  
Adaptive Cytoprotection ◽  
Rat Gastric Mucosa ◽  
Mild Irritant

Gastric resistance to acid: is the "mucus-bicarbonate barrier" functionally redundant?

1989 ◽  
Vol 256 (1) ◽  
pp. G31-G38 ◽  
Author(s):  
J. L. Wallace
Keyword(s):  
Gastric Mucosa ◽  
Protein Concentration ◽  
Ex Vivo ◽  
Mucosal Surface ◽  
Ph Gradient ◽  
Surface Epithelium ◽  
Acid Solutions ◽  
Rat Stomach ◽  
Functional Importance ◽  
Mucolytic Agents

The functional importance of the "mucus-bicarbonate barrier" in protecting the gastric mucosa against injury by acid or pepsin was examined using an ex vivo gastric chamber preparation in the rat. Conditions were created such that the effectiveness of a mucus-stabilized pH gradient on the mucosal surface would be minimized. Thus solutions of hydrochloric acid of pH 1.3 or 0.8 were applied to the mucosal surface and continually stirred for 60 min. By use of an antimony pH microelectrode, these concentrations of acid were shown to dissipate the pH gradient on the mucosal surface within 5 min. The effects of addition of the mucolytic agents, pepsin or N-acetylcysteine, to both acid solutions were also assessed. Finally, the ability of the mucosa to resist injury by acid after disruption of the surface epithelium (with hypertonic saline) was examined. Exposure to the acid solutions, with or without added mucolytic agents, was without damaging effects on the mucosa, as assessed macroscopically, histologically, or by measurement of transmucosal potential difference and luminal protein concentration. Conversely, disruption of the surface epithelium rendered the mucosa significantly more susceptible to the damaging actions of acid. These results therefore demonstrate that under conditions in which a pH gradient on the mucosal surface was no longer detectable, the mucosa was resistant to injury by acid. In the undamaged rat stomach, therefore, the mucus-bicarbonate barrier may be functionally redundant.

Oxidative and haemostatic effects of copper, manganese and mercury, alone and in combination at physiologically relevant levels: An ex vivo study

2018 ◽  
Vol 38 (4) ◽  
pp. 419-433 ◽  
Author(s):  
MJ van Rensburg ◽  
M van Rooy ◽  
MJ Bester ◽  
JC Serem ◽  
C Venter ◽  
...  
Keyword(s):  
World Health Organization ◽  
Ex Vivo ◽  
Thrombus Formation ◽  
World Health ◽  
Anthropogenic Activity ◽  
Increased Risk ◽  
Metal Levels ◽  
The World ◽  
Subsequent Exposure ◽  
Health Organization

Water contamination with metals due to anthropogenic activity is increasing and subsequent exposure increases the risk of associated toxicity. Exposure is not limited to a single metal but usually involves mixtures of different metals at different concentrations. Little is known about the contribution of this type of exposure, in humans, to the development of non-communicable diseases such as cardiovascular disease, and an increased risk to thrombosis. The World Health Organization has established limits for metal levels in drinking water and this includes levels for copper (Cu), manganese (Mn) and mercury (Hg). In this study, at 100X these limits, the ability of the metals’ oxidative effects as catalysts of the Fenton reaction and/or ability to bind glutathione (GSH) were determined. The haemostatic effects of these metals, alone and in combination, at the World Health Organization limit were then evaluated. The ultrastructural and viscoelastic alterations of exposed ex vivo whole blood were also evaluated using scanning electron microscopy and thromboelastography® (TEG), respectively. Cu, alone and in combination with Mn and/or Hg, induced hydroxyl radical formation and reduced GSH levels. Ex vivo exposure caused deformation of erythrocytes and accelerated platelet activation especially for Cu, alone and in combination, with Mn. Reduction in the lysis potential of the clot was also observed for all combinations, especially Cu in combination with Hg as well as Mn alone. Although the TEG findings were not statistically significant, the trends indicate that the exposure to these metals, alone and in combination, adversely affects thrombus formation in ex vivo blood, thereby potentially increasing the risk in exposed individuals for thrombosis.

Glucocorticoid-Induced Differential Expression of the Sialylated and Nonsialylated Lewisa Epitopes and Respective Binding Sites in Human Nasal Polyps Maintained under ex vivo Tissue Culture Conditions

2002 ◽  
Vol 111 (12) ◽  
pp. 1097-1107 ◽  
Author(s):  
Carine Delbrouck ◽  
Nikolay E. Nifant'ev ◽  
Hans-Joachim Gabius ◽  
Herbert Kaltner ◽  
Nicolai V. Bovin ◽  
...  
Keyword(s):  
Tissue Culture ◽  
Adhesion Molecule ◽  
Binding Sites ◽  
Nasal Polyps ◽  
Ex Vivo ◽  
Culture Conditions ◽  
Intercellular Adhesion Molecule ◽  
Surface Epithelium ◽  
Computer Assisted ◽  
Ex Vivo Tissue

We characterized the anti-inflammatory effects of budesonide on the expression of adhesion molecules involving Lewisa (Lea) epitope, its sialylated derivative (sLea), and their respective binding sites in human nasal polyposis. By computer-assisted microscopy, we quantitatively characterized the level of histochemical expression of L- and P-selectins, sialylated and nonsialylated Lea epitopes, and their respective binding sites in both surface epithelium and glandular epithelium of human nasal polyps obtained from surgical resection, maintained under ex vivo tissue culture conditions for 24 hours, and treated or not with budesonide. Intercellular adhesion molecule 1 (ICAM-1) and vascular cell adhesion molecule 1 (VCAM-1) were chosen as methodological controls, because data already published in the literature clearly indicated budesonide-mediated effects on ICAM-1 and VCAM-1 levels of expression. The present data show that budesonide significantly modified the levels of expression of ICAM-1 and VCAM-1, and to a lesser extent that of P-selectin, in the surface and glandular epithelia. Budesonide markedly decreased the levels of expression of the binding sites for both Lea and sLea, while those of Lea and sLea remained globally unchanged. In conclusion, the present study documents that glucocorticoid-induced effects can encompass receptors for Lea epitopes different from E- and P-selectins on epithelial cells of human nasal polyps.

Omeprazole and cimetidine versus pentagastrin in canine ex vivo gastric chamber

1989 ◽  
Vol 256 (2) ◽  
pp. G390-G395 ◽  
Author(s):  
K. R. Larsen ◽  
M. M. Ives ◽  
N. F. Jensen ◽  
E. Carlsson ◽  
H. Larsson
Keyword(s):  
Blood Flow ◽  
Oxygen Consumption ◽  
Ex Vivo ◽  
Venous Blood ◽  
Blood Gases ◽  
Mucosal Blood Flow ◽  
Systemic Blood Pressure ◽  
Potential Difference ◽  
Gastric Blood Flow ◽  
Dose Dependent

The effects of acid inhibitory doses of omeprazole were compared with equieffective doses of cimetidine in the canine ex vivo stomach model (n = 30). Systemic blood pressure, temperature, stomach fluid and ion fluxes, potential difference, blood flow rates, and arterial and venous blood gases were monitored during each of nine 30-min periods. Two resting periods preceded seven periods of pentagastrin stimulation. During the last four of these, the drug effect was recorded (cimetidine 1.2 or 4.8 mumol.kg-1.h-1; omeprazole 0.3, 0.6, or 1.2 mumol/kg). Omeprazole (1.2 mumol/kg) produced 100% inhibition of stimulated acid efflux, no significant decrease in total gastric blood flow (venous outflow), 90% return of potential difference (PD) toward resting values, and a 55% reduction in stimulated oxygen consumption. Omeprazole also showed a dose-dependent K+ efflux at the two lower doses. Cimetidine (4.8 mumol.kg-1.h-1) given during pentagastrin stimulation showed a 70% decrease in total gastric blood flow, a 40% return of PD toward resting, and a 77% reduction in stimulated oxygen consumption. Neither drug showed significant changes in mucosal blood flow from resting values, thus supporting the principle that changes in gastric acid secretion and changes in blood flow are not necessarily correlated.

scholarly journals Native and recombinant Slc26a3 (downregulated in adenoma, Dra) do not exhibit properties of 2Cl−/1HCO3− exchange

2011 ◽  
Vol 300 (2) ◽  
pp. C276-C286 ◽  
Author(s):  
Seth L. Alper ◽  
Andrew K. Stewart ◽  
David H. Vandorpe ◽  
Jeffrey S. Clark ◽  
R. Zachary Horack ◽  
...  
Keyword(s):  
Membrane Potential ◽  
Ex Vivo ◽  
Short Circuit ◽  
Outward Current ◽  
Anion Channel ◽  
Short Circuit Current ◽  
Surface Epithelium ◽  
Steady State Current ◽  
Health And Disease ◽  
Secondary Membrane

The recent proposal that Dra/Slc26a3 mediates electrogenic 2Cl−/1HCO3− exchange suggests a required revision of classical concepts of electroneutral Cl− transport across epithelia such as the intestine. We investigated 1) the effect of endogenous Dra Cl−/HCO3− activity on apical membrane potential ( Va) of the cecal surface epithelium using wild-type (WT) and knockout (KO) mice; and 2) the electrical properties of Cl−/(OH−)HCO3− exchange by mouse and human orthologs of Dra expressed in Xenopus oocytes. Ex vivo 36Cl− fluxes and microfluorometry revealed that cecal Cl−/HCO3− exchange was abolished in the Dra KO without concordant changes in short-circuit current. In microelectrode studies, baseline Va of Dra KO surface epithelium was slightly hyperpolarized relative to WT but depolarized to the same extent as WT during luminal Cl− substitution. Subsequent studies indicated that Cl−-dependent Va depolarization requires the anion channel Cftr. Oocyte studies demonstrated that Dra-mediated exchange of intracellular Cl− for extracellular HCO3− is accompanied by slow hyperpolarization and a modest outward current, but that the steady-state current-voltage relationship is unaffected by Cl− removal or pharmacological blockade. Further, Dra-dependent 36Cl− efflux was voltage-insensitive in oocytes coexpressing the cation channels ENaC or ROMK. We conclude that 1) endogenous Dra and recombinant human/mouse Dra orthologs do not exhibit electrogenic 2Cl−/1HCO3− exchange; and 2) acute induction of Dra Cl−/HCO3− exchange is associated with secondary membrane potential changes representing homeostatic responses. Thus, participation of Dra in coupled NaCl absorption and in uncoupled HCO3− secretion remains compatible with electroneutrality of these processes, and with the utility of electroneutral transport models for predicting epithelial responses in health and disease.

Simultaneous measurement of cell loss and gastric potential difference in the rat: Effects of short-term fasting

1979 ◽  
Vol 57 (7) ◽  
pp. 745-748 ◽  
Author(s):  
R. K. Harding ◽  
G. P. Morris ◽  
C. Doan
Keyword(s):  
Simultaneous Measurement ◽  
Simple Technique ◽  
Ex Vivo ◽  
Cell Loss ◽  
Potential Difference ◽  
Short Term ◽  
Gastric Potential Difference

These experiments utilized ex vivo gastric chamber preparations in both fed rats and rats fasted for 14–18 h. A new, simple technique is described for the quantification of cells in small volumes of fluid. The data indicate that exposure to solutions of 50 mM HCl was accompanied by greater cell loss in fasted vs. fed animals. The gastric potential differences of mucosae exposed to Ringer's mammalian saline, and subsequently to 50 mM HCl, were consistently at least 10 mV more negative in fasted animals.

scholarly journals Vinegar is a Dietary Mild Irritant to the Rat Gastric Mucosa

1986 ◽  
Vol 41 (1) ◽  
pp. 101-108 ◽  
Author(s):  
Youichi NOBUHARA ◽  
Koji TAKEUCHI ◽  
Susumu OKABE
Keyword(s):  
Gastric Mucosa ◽  
Rat Gastric Mucosa ◽  
Mild Irritant
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