Arecae pericarpium extract induces porcine lower-esophageal-sphincter contraction via muscarinic receptors

Background Gastroesophageal reflux disease (GERD) is associated with lower esophageal sphincter (LES) incompetence. In some patients, GERD is refractory to acid reduction therapy which is the main treatment for GERD. So far, medications that can increase LES tone are few. Arecae pericarpium (A. pericarpium) is a medication in Traditional Chinese Medicine known to promote intestinal motility. Methods We investigated the effect of A. pericarpium extracts on porcine LES motility. In addition, we used tetrodotoxin (TTX) and atropine to study the underlying mechanism of A. pericarpium extracts-induced contractions of LES. Results The results of this study showed that A. pericarpium extracts and their main active ingredient, arecoline, can induce the contractions of porcine LES sling and clasp muscles in a dose-response manner. TTX did not have an inhibitory effect on the contractions induced by A. pericarpium extracts and arecoline in LES. However, atropine significantly inhibited A. pericarpium extracts- and arecoline-induced contractions of LES. Conclusion A. pericarpium extracts can induce the contractions of porcine LES in a dose dependent manner, possibly through muscarinic receptors, and hence, may be worth developing as an alternative therapy for GERD.

Autoantigen characterization in the lower esophageal sphincter muscle of patients with achalasia.

OBJECTIVE: To characterize in sera anti-myenteric autoantibody profiles and in tissues MMP-9 proteoforms towards the identification of possible autoantigenic proteins in the muscle of the lower esophageal sphincter (LES) of achalasia patients. METHODS: Biopsies of the LES muscle from 36 achalasia patients, 6 esophagogastric junction outflow obstruction (EGJOO) patients, and 16 transplant donors (TD) were compared in a blind cross-sectional study. Histological characteristics such as inflammation, fibrosis, presence of ganglion cells, cells of Cajal, GAD65, PNMA2, S100, P substance, and MMP-9 proteforms in tissue were assessed by H&E and Picro-Sirius Red stainings, and immunohistochemistry analysis. Antineuronal antibodies (amphiphysin, CV2, and PNMA2 (Ma2/Ta)), onconeural antigens (Ri, Yo, and Hu), recoverin, SOX-1, titin, zic4, GAD65, and Tr (DNER) were evaluated by immunoblot/line assay. RESULTS: Tissue of achalasia patients had heterogeneous inflammatory infiltrates with fibrosis and contrasting higher levels of activated MMP-9 compared with EGJOO and TD. Moreover, lower ganglion cell percentages and cell of Cajal percentages were determined in esophageal tissues of achalasia patients vs. TD. In addition, tissue of achalasia patients had higher GAD65 and PNMA2 protein expression vs. EGJOO. Unexpectedly, these proteins were absent in TD tissue. S100 and P substance had similar expression levels in tissues of achalasia patients vs.TD and EGJOO. Most of the achalasia sera had anti-GAD65 (83%) and anti-PNMA2 (90%) autoantibodies vs. EGJOO (17% and 33%, respectively) and healthy volunteers (10% and 0%, respectively). CONCLUSION: Tissue-specific ectopic expression of GAD65 and PNMA/Ta2 and active MMP-9, associated with the presence of specific autoantibodies directed against these proteins, might participate in the pathophysiology of achalasia triggering and/or perpetuating autoimmune disease.

The Impact of Bariatric Procedures on Esophageal Motility

Bariatric operations may cause or cure gastroesophageal reflux disease (GERD). The comprehension of esophageal motility following different types of bariatric procedures may help understand the relationship between GERD and bariatric surgery. This review focused on the impact of bariatric procedures on esophageal motility. We found that lower esophageal sphincter resting pressure is increased after adjustable gastric banding; is unaltered or decreased after Roux-en-Y gastric bypass; and is decreased after sleeve gastrectomy. Lower esophageal sphincter relaxation may be abnormal after all these procedures. Esophageal body contractility is worsened after sleeve gastrectomy.