T. Zbroch

Esophagoprotective potential of cisapride: an additional benefit for gastroesophageal reflux disease

Cisapride is a novel prokinetic agent thatreleases acetylcholine at the level of the myentericplexus. Acetylcholine also plays a role in the secretoryfunction of salivary glands evoked by intraesophagal mechanical and chemical stimulation, mediatedthrough the esophagosalivary reflex. The impact,however, of cisapride on salivary protective componentsmediated by esophagosalivary reflex remains unknown. Therefore, we have studied salivary pH,bicarbonate, nonbicarbonate, glycoconjugate, protein,EGF, TGF-α, and PGE2 before and afterthe administration of cisapride. The study was conductedin 20 asymptomatic volunteers (9 women and 11 men, mean age 36,range 26-52). Salivary secretions were collected underbasal conditions and during masticatory, mechanical, andchemical stimulation before and after four days of cisapride administration (10 or 20 mg fourtimes a day). Cisapride administration resulted in a 45%increase in salivary volume during the basal condition(P < 0.01), a 32% increase during mastication (P < 0.05), a 53% increase during mechanical(P < 0.05), and a 51% increase during chemical (P< 0.01) stimulation. Cisapride administrationresulted also in a significant increase in salivaryprotein output (P < 0.05), salivary bicarbonate (P <0.05), and nonbicarbonate buffers (P < 0.05), andsalivary EGF (P < 0.05). Salivary glycoconjugatesignificantly increased only during mechanicalstimulation with the catheter and at the end of the esophageal perfusionprocedure (P < 0.05). Although a similar trend wasalso recorded during the analysis of salivaryPGE2, this difference did not reachstatistical significance. Salivary pH and TGF-α before and after cisaprideadministration remained unchanged. The stimulatoryimpact of cisapride on salivary volume and inorganic(bicarbonate and nonbicarbonate buffers) and organic(protein, glycoconjugate, and EGF) protective componentswould benefit patients with GERD and would also bepotential therapy for xerostomia.

The potential role of the esophageal pre-epithelial barrier components in the maintenance of integrity of the esophageal mucosa in patients with endoscopically negative gastroesophageal reflux disease

OBJECTIVE:Patients with gastroesophageal reflux disease (GERD) accompanied by erosive reflux esophagitis (RE) exhibit an impairment within the esophageal pre-epithelial barrier protective components that may facilitate the development and/or progression of the mucosal injury. Little is known, however, whether such impairment is a general phenomenon affecting all patients with GERD or whether this is a characteristic feature only of patients with erosive RE. We therefore studied the rate of secretion of esophageal inorganic and organic protective factors in patients with endoscopically negative [E (−)] GERD and compared these results with the corresponding values in asymptomatic volunteers (CTRL).METHODS:The study was conducted on 33 white asymptomatic volunteers and 10 white patients with a long history of GERD confirmed by 24-h pH monitoring and a grossly negative upper endoscopy. Esophageal secretion was collected during mucosal exposure to NaCl, HCl, HC/pepsin and NaCl using the esophageal perfusion catheter. In collected samples all investigated parameters were measured.RESULTS:The pH of esophageal secretion and its content of bicarbonate, EGF, and PGE2 in patients with E (−) GERD and asymptomatic volunteers were similar. Unexpectedly, the rate of esophageal glycoconjugate (predominantly mucin) secretion was significantly higher in patients with E (−) GERD than in controls during perfusion with HCl (p < 0.05). Furthermore, secretion of protein in patients with E (−) GERD was significantly higher than in the control group during the mucosal exposure to HCl/Pepsin (p < 0.05). The nonbicarbonate buffer secretion during perfusion with HCl and HCl/Pepsin as well as the rate of esophageal TGFα output during infusion of final saline in patients with E (−) GERD were significantly lower than in CTRL group (p < 0.05).CONCLUSIONS:Our data indicate that patients with E (−) GERD have an esophageal secretory potential, in terms of glycoconjugate and protein, higher than that in asymptomatic controls. This phenomenon in patients with E (−) GERD may, by enhancing the quantity of the esophageal pre-epithelial barrier, help to prevent the development of erosive esophagitis. A significantly lower esophageal secretory response in patients with E (−) GERD in terms of nonbicarbonate buffers and TGFα may facilitate the development of GERD symptoms and histological changes of GERD, respectively.

A distinct salivary secretory response mediated by the esophago-salivary reflex in patients with Barrett's esophagus: Its potential pathogenetic implications

PURPOSEnA significantly compromised epidermal growth factor (EGF) secretion by basal parotid saliva may contribute to the development of Barretts esophagus (BE). The rate of secretion of EGF as well as a wide spectrum of protective factors in total basal and stimulated saliva in BE patients remains to be explored. We therefore studied the rate of secretion of salivary buffers, glycoconjugate, protein, EGF, transforming growth factor α (TGFα) and prostaglandin E₂ (PGE₂), evoked by esophago-salivary reflex, in patients with BE and controls (CTRL).nnnMATERIAL/METHODSnSalivary secretion was collected during basal condition, mastication, and intraesophageal mechanical and chemical stimulations respectively, mimicking the natural gastroesophageal reflux scenario.nnnRESULTSnSalivary pH in BE was significantly lower than in controls during mechanical (p<0.001) and chemical stimulations (p<0.001). Bicarbonate and protein outputs in BE were significantly lower during mechanical (p<0.05) and chemical stimulations (p<0.01). The non-bicarbonate and glycoconjugate outputs in BE were lower during chemical stimulation (p<0.05) and during mechanical (p<0.05) and chemical stimulations (p<0.05) respectively. The rate of salivary EGF output in BE was significantly lower during mechanical stimulation (p<0.05). We observed a higher TGFα output during mastication (p<0.05) and PGE2 secretion during basal and masticatory condition (p<0.05) in BE.nnnCONCLUSIONSnPatients with BE demonstrated significantly compromised salivary pH and rate of secretion of bicarbonate, non-bicarbonate, glycoconjugate, protein and EGF. This impairment could potentially predispose to the development of accelerated esophageal mucosal injury. Potential restoration of this impairment by masticatory stimulation of salivary secretion using sugarless chewing gum justifies further clinical exploration.

Augmented salivary protective potential: Is it one explanation to the lower prevalence of reflux esophagitis and complications in African-Americans?

It is well known that African-Americans (AA) are less likely to develop reflux esophagitis (RE) and its complications than Caucasians (C). Since salivary protective components play a key role in the maintenance of the integrity of the esophageal mucosa, we hypothesized that AA may benefit from their higher protective quality of saliva. Aims: 1. To assess content of salivary glycoconjugate (mucin), protein, bicarbonate, non-bicarbonate, TGFa, and PGE 2 in AA. 2. To compare these results with corresponding values in a C population, comparable in terms of age and gender. Subjects & Methods: The study was approved by IRB and conducted in 27 AA (12F and 15M, mean age of 41, range 29-52) and in 39 C (16F and 23M, mean age of 39, range 26-56) asymptomatic volunteers. Salivary secretions were collected under basal conditions, during mastication, and during intraesophageal mechanical and chemical stimulation, mimicking the gastroesophageal reflux scenario by using an esophageal perfusion catheter (Wilson-Cook Med. Inc., NC). Salivary glycoconjugate (mucin) and protein in salivary secretion were quantitated using PAS and Lowry methods, respectively. Salivary bicarbonate and non-bicarbonate were measured using Titra-Lab (Radiometer America, IL), whereas TGFa, and PGE 2 by RIA (Amersham, IL) and analyzed statistically by E-Stat (Jandel Sci. CA). Results: African-Americans secreted significantly more of salivary glycoconjugate (P < 0.01), protein (P < 0.05), and non-bicarbonate buffers (P < 0.01) in basal conditions; glycoconjugate (P < 0.05), protein (P < 0.05), and non-bicarbonate (P < 0.05) during mastication; glycoconjugate (P < 0.05), protein (P < 0.01), bicarbonate (0.05), non-bicarbonate (P < 0.01), and TGFa (P < 0.001) during intraesophageal mechanical stimulation; protein (P < 0.0001), bicarbonate (P < 0.05), non-bicarbonate (P < 0.05), and TGFa (P < 0.001) during intraesophageal chemical stimulation than Caucasians. Conc_!usion: • These data indicate that a significantly enhanced secretion of salivary protective factors in AA may prevent the development of esophageal mucosal pathology and subsequent complications during episodes of GER.

Salivary protective potential is significantly enhanced by stimulation induced both by mastication and esophago-salivary reflex: its clinical significance

Purpose: An increase in the rate of salivary secretion during heartburn symptoms in patients with GERD is a well established phenomenon. Salivary secretion stimulated by mastication exhibits a significantly enhanced protective potential (Gastroenterology, 110:675–81, 1996). Little is known, however, regarding the interrelationship between the rate of secretion of each individual protective factor in basal conditions and during stimulation. Therefore, the aim of the study was to explore the correlation between the rate of secretion of salivary bicarbonate (BIC), non-bicarbonate (NBIC), protein, glycoconjugate, epidermal growth factor (EGF), transforming growth factor a (TGF ) and prostaglandin E2 (PGE 2) in basal and stimulated (by mastication or esophago-salivary reflex) conditions.