Esophageal Epithelial Resistance and Lower Esophageal Sphincter Muscle Contraction Increase in a Chronic Diabetic Rabbit Model.

BACKGROUND: Esophageal motility disorders and possibly gastroesophageal reflux disease are common in patients with diabetes mellitus. AIMS: We aimed to investigate both the electrophysiological characteristics of the esophageal epithelium and the contractility of the lower esophageal sphincter (LES) muscle in alloxane-induced diabetic rabbits. METHODS: Electrophysiological properties were measured using an Ussing chamber method. An acid-pepsin model was employed with pH 1.7 or weakly acidic (pH 4) Ringer and/or pepsin. Smooth muscle strips of the LES were mounted in an isolated organ bath. Contractile responses to an electrical field stimulation and cumulative concentrations of acetylcholine were recorded. Contractility of the muscle strips were tested in the presence of Rho-kinase inhibitor (Y-27632) and nonspecific nitric oxide inhibitor (L-NAME). RESULTS: The resistance of diabetic tissue perfused in the pH 1.7 Ringer decreased 17 %; pepsin addition decreased it by 49 %. The same concentrations caused a more distinct loss of resistance in the control tissues (22 and 76 %, p < 0.05). The perfusion of tissues in increased concentrations of luminal and serosal glucose did not change the tissue resistance and voltage. Diabetes significantly increased both the electrical field stimulation and acetylcholine-induced contractions in the LES muscle strips (p < 0.01). Incubation with Y-27632 significantly decreased the acetylcholine-induced contractions in a concentration-dependent manner (p < 0.01). CONCLUSIONS: The acid-pepsin model in the diabetic rabbit esophageal tissue had less injury compared with the control. The diabetic rabbit LES muscle had higher contractility, possibly because of the activation of the Rho-Rhokinase pathway. Our results show that in a chronic diabetic rabbit model the esophagus resists reflux by activating mechanisms of mucosal defense and increasing the contractility of the LES.

The additive effect of ethanol and extract of cigarette smoke on rabbit esophagus epithelium.

AIM: The combination of alcohol and smoking takes a place in the epidemiology and pathogenesis of gastroesophageal reflux disease and squamous cancers of the esophagus. Therefore, a study was designed to assess the impact of these agents alone or in combination on the structure and function of squamous epithelium of rabbit esophagus. METHODS: Rabbit esophageal epithelium was mounted in Ussing Chambers, exposed luminally for ethanol (1-10%), extract of cigarette smoke (EOCS) and combinations or sequential application of these agents. An in-vivo model was also used to mimic conditions more representative of human alcohol consumption. RESULTS: Ethanol (1-10%) dose dependently decreased tissue resistance. Extract of cigarette smoke caused a reduction on transepithelial potential difference (PD), short circuit current. Combinations of EOCS, ethanol (5-10% EtOH and EOCS 1-2) showed a more pronounced decrease than agents alone, mainly the result of EOCS. In vivo studies showed that EOCS administration dropped PD dose dependently. In-vivo 10% EtOH, EOCS-2 dropped PD (55%) similar to in-vitro 5% EtOH, EOCS-1. The effect was clearly additive; boluses of 10% ethanol (36%) and EOCS-2 (17%) decreased PD and combination of agents resulted in a 55% drop on PD which is a very similar decrease compared to the sum of the separate effects of agents (53%). CONCLUSION: Ethanol affected the barrier and cigarette smoke altered ion transport on rabbit esophageal epithelium under conditions reflecting human consumption. Results were consistent with in vivo and in vitro conditions except higher concentrations were needed in vivo. When applied, these agents showed an additive effect. Ethanol predisposed the tissue to the effect of EOCS.

Validation of Peptest™ in Patients with Gastro-Esophageal Reflux Disease and Laryngopharyngeal Reflux Undergoing Impedance Testing.

BACKGROUND AND AIMS: Pepsin in the gastric refluxate is a marker for a prior reflux event and rapid detection might be achieved using the Peptest™, an in vitro diagnostic medical device. The aim of this study was to validate the use of Peptest™ to reliably diagnose reflux in patients with gastro-esophageal reflux disease (GERD) and laryngopharyngeal reflux (LPR) disease diagnosed with multichannel intraluminal impedance/ pHmetry (MII-pH). METHODS: 20 reflux patients were recruited of whom 10 had classical GERD and 10 had LPR. All patients underwent MII-pH and provided expectorated saliva samples when a MII-pH reflux event was observed, or reflux symptoms were experienced, and all were tested for the presence of pepsin using the Peptest™. RESULTS: Pepsin was detected in 31 out of 45 samples (68.9%). At least 1 positive pepsin result was seen in 16 patients (80%) and this was the same, irrespective of the GERD or LPR diagnosis. Peptest™ had a positive predictive value of 69% to detect MII-pH reflux events. CONCLUSIONS: Peptest™ is a good first-line diagnostic procedure to use in reflux sufferers to confirm the presence of reflux.

Tissue resistance in the normal and diseased esophagus.

This paper presents commentaries on reflux-induced injury of human esophageal epithelium; inflammation in human reflux esophagitis; motor consequences of reflux-induced inflammation in esophageal epithelium; the microscopic morphology of esophageal squamous epithelium; intraluminal impedance in the evaluation of the esophageal mucosa; endoscopic tissue morphology of esophageal squamous epithelium; and the developmental biology of esophageal squamous epithelium.

Dietary Phytosterols Protective Against Peptic Ulceration.

BACKGROUND: In developing countries the prevalence of duodenal ulceration is related to the staple diet and not to the prevalence of Helicobacter pylori. Experiments using animal peptic ulcer models show that the lipid fraction in foods from the staple diets of low prevalence areas gives protection against ulceration, including ulceration due to non-steroidal anti-inflammatory drugs (NSAIDs), and also promotes healing of ulceration. The lipid from the pulse Dolichos biflorus (Horse gram) was highly active and used for further investigations. Further experiments showed the phospholipids, sterol esters and sterols present in Horse gram lipid were gastroprotective. Dietary phospholipids are known to be protective, but the nature of protective sterols in staple diets is not known. The present research investigates the nature of the protective phytosterols. METHODS: Sterol fractions were extracted from the lipid in Dolichos biflorus and tested for gastroprotection using the rat ethanol model. The fractions showing protective activity were isolated and identification of the components was investigated by Gas Chromatography-Mass Spectrometry (GC-MS). RESULTS: The protective phytosterol fraction was shown to consist of stigmasterol, ß-sitosterol and a third as yet unidentified sterol, isomeric with ß-sitosterol. CONCLUSIONS: Dietary changes, affecting the intake of protective phospholipids and phytosterols, may reduce the prevalence of duodenal ulceration in areas of high prevalence and may reduce the incidence of recurrent duodenal ulceration after healing and elimination of Helicobacter pylori infection. A combination of phospholipids and phytosterols, such as found in the lipid fraction of ulceroprotecive foods, may be of value in giving protection against the ulcerogenic effect of NSAIDs.