Biomedical subjects

Roy C Orlando

Publications and source records attributed to Roy C Orlando.

5 recordsLinked to original sources

PubMed2002

Pathogenesis of gastroesophageal reflux disease.

The pathophysiology of GERD involves contact of the esophageal epithelium with acid/pepsin in the refluxate. For this contact to occur with sufficient duration, there must be a combination of defects in antireflux and luminal clearance mechanisms for acid/pepsin to overwhelm an intact epithelium, or defects within the epithelium develop that subsequently enable normal acid contact times to become damaging to the epithelium. In either case, the final common pathway is damage to the esophageal epithelium--damage that is reflected in the development of heartburn, esophageal necrosis and inflammation, or both.

Esophageal Motility Disorders↗

PubMed2002

Effect of acid perfusion on passive electrophysiological properties of rabbit esophagus in vivo.

In the present paper we studied early acid-induced changes in the passive electrical properties of the rabbit esophageal epithelium in vivo by measurements of the transluminal potential difference (PD) during acid perfusion and by estimating the transmucosal electrical resistance (Rm) using cable analysis. Perfusion with acid (pH 1) for 45 min produced a rapid (<1 min) negative shift in the lumen-negative PD followed by a slow lumen-negative drift. The acid-induced change in PD was dependent on the accompanying anion, the largest anion (sulfate) producing the largest change. The acid-induced changes in PD were parallelled by reductions in Rm, these reductions also being dependent on the accompanying anion. Interpretation of resistance and net current (estimated by Ohm's law) time curves suggest that the initial acid-induced changes of the PD reflect properties of the naive mucosa whereas the later drift will reflect a diffusion driven increase in transmucosal proton permeability. Further, coapplication of the protective drug sucrose octasulfate attenuated the hydrochloric acid-induced changes of all measured and estimated electrophysiological parameters. The electrophysiological results were to some extent corroborated by light microscopic findings, although no large acid-induced change in mucosal appearance was observed.

Action Potentials↗

PubMed2002

Chloride transport in rabbit esophageal epithelial cells.

We investigated Cl(-) transport pathways in the apical and basolateral membranes of rabbit esophageal epithelial cells (EEC) using conventional and ion-selective microelectrodes. Intact sections of esophageal epithelium were mounted serosal or luminal side up in a modified Ussing chamber, where transepithelial potential difference and transepithelial resistance could be determined. Microelectrodes were used to measure intracellular Cl(-) activity (a), basolateral or apical membrane potentials (V(mBL) or V(mC)), and the voltage divider ratio. When a basal cell was impaled, V(mBL) was -73 +/- 4.3 mV and a(i)(Cl) was 16.4 +/- 2.1 mM, which were similar in presence or absence of bicarbonate. Removal of serosal Cl(-) caused a transient depolarization of V(mBL) and a decrease in a(i)(Cl) of 6.5 +/- 0.9 mM. The depolarization and the rate of decrease of a(i)(Cl) were inhibited by approximately 60% in the presence of the Cl(-)-channel blocker flufenamate. Serosal bumetanide significantly decreased the rate of change of a(i)(Cl) on removal and readdition of serosal Cl(-). When a luminal cell was impaled, V(mC) was -65 +/- 3.6 mV and a was 16.3 +/- 2.2 mM. Removal of luminal Cl(-) depolarized V(mC) and decreased a by only 2.5 +/- 0.9 mM. Subsequent removal of Cl(-) from the serosal bath decreased a(i)(Cl) in the luminal cell by an additional 6.4 +/- 1.0 mM. A plot of V(mBL) measurements vs. log a(i)(Cl)/log a(o)(Cl) (a(o)(Cl) is the activity of Cl(-) in a luminal or serosal bath) yielded a straight line [slope (S) = 67.8 mV/decade of change in a(i)(Cl)/a(o)(Cl)]. In contrast, V(mC) correlated very poorly with log a/a (S = 18.9 mV/decade of change in a/a). These results indicate that 1) in rabbit EEC, a(i)(Cl) is higher than equilibrium across apical and basolateral membranes, and this process is independent of bicarbonate; 2) the basolateral cell membrane possesses a conductive Cl(-) pathway sensitive to flufenamate; and 3) the apical membrane has limited permeability to Cl(-), which is consistent with the limited capacity for transepithelial Cl(-) transport. Transport of Cl(-) at the basolateral membrane is likely the dominant pathway for regulation of intracellular Cl(-).

4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid↗

PubMed2002

Regulatory volume decrease in human esophageal epithelial cells.

In vivo human esophageal epithelial cells are regularly exposed to hyposmolal stress. This stress, however, only becomes destructive when the surface epithelial cell (barrier) layers are breached and there is contact of the hyposmolal solution with the basolateral cell membranes. The present investigation was designed to examine the effects of hyposmolal stress in the latter circumstance using as a model for human esophageal epithelial cells the noncancer-derived HET-1A cell line. Cell volume and the response to hyposmolal stress in suspensions of HET-1A cells were determined by cell passage through a Coulter Counter Multisizer II. HET-1A cells behaved as osmometers over the range of 280 to 118 mosmol/kg H(2)O with rapid increases in cell volume < or = 15-20% above baseline. Following swelling, the cells exhibited regulatory volume decrease (RVD), restoring baseline volume within 30 min, despite continued hyposmolal stress. With the use of pharmacologic agents and ion substitutions, RVD appeared to result from rapid activation of parallel K(+) and Cl(-) conductance pathways and this was subsequently joined by activation of a KCl cotransporter. Exposure to hyposmolal stress in an acidic environment, pH 6.6, inhibited, but did not abolish, RVD. These data indicate that human esophageal epithelial cells can protect against hyposmolal stress by RVD and that the redundancy in mechanisms may, to some extent, serve as added protection in patients with reflux disease when hyposmolal stress may occur in an acidic environment.

4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid↗

PubMed2002

Mechanisms of epithelial injury and inflammation in gastrointestinal diseases.

Using Barrett's esophagus and Crohn's disease as models of gastrointestinal disorders, a number of key mechanisms of cell injury and death and chronic inflammation are reviewed. Among them are the roles of impaired osmoregulation, elevated cytosolic calcium, activation of the mitochondrial permeability transition and levels of cytosolic adenosine triphosphate as determinates of cell death as well as the role of inflammatory cells, cytokines, NOD2 gene products, and reactive oxygen species in chronic inflammation. Further, the basis for the link between inflammation and cancer risk in Barrett's esophagus and Crohn's disease is described.

Adenocarcinoma↗