Protective effect of lactoferrin on acute acid reflux-induced esophageal mucosal damage.

BACKGROUND/AIMS: The natural immunomodulator lactoferrin is known to possess anti-inflammatory effects. However, there have been no studies examining the mode of action of lactoferrin in protecting the esophageal mucosa against damage. We investigated the effect of lactoferrin on gastric acid secretion and in protecting against acute acid reflux-induced esophagitis in rats. METHODOLOGY: Male Wistar rats aged 8 weeks, weighing 210-240 g, were used for all the experiments. A gastric perfusion system was installed using the method of Ghosh et al. Lactoferrin was administered once via the caudate vein, starting 24 hours before an acute acid reflux (treatment mode), or saline (control). Statistical comparison of the parameters between the two test conditions was performed. RESULTS: No significant differences in basal or stimulated gastric acid secretion, or in the serum gastrin level were observed between the two test conditions. Esophageal damage was attenuated by lactoferrin in a dose-dependent manner, as reflected by the improvement in the esophageal tissue weight and macroscopic scores. Significant reductions in the histological scores, myeloperoxidase activity and the levels of proinflammatory cytokines, tumor necrosis factor-α and interleukin-1ß were also observed following lactoferrin administration. CONCLUSIONS: We concluded that lactoferrin exerts a protective effect against acute acid reflux-induced esophageal damage in rats.

mRNA expression of inducible nitric oxide synthase, endothelial nitric oxide synthase and vascular endothelial growth factor in esophageal mucosa biopsy specimens from patients with reflux esophagitis.

BACKGROUND/AIMS: Nitric oxide (NO) production is elevated in the intestine and may contribute to intestinal injury during inflammation. However, how the expression of inducible NO synthase (iNOS) mRNA and endothelial NO synthase (eNOS) mRNA in the esophageal mucosa contribute to mucosal damage caused by reflux esophagitis remains unknown. Since vascular endothelial growth factor (VEGF) exerts its action on microcirculation, contributing to angiogenesis and inflammation, we examined the role of VEGF together with iNOS and eNOS on development of reflux esophagitis. METHODOLOGY: The mRNA expression levels of iNOS, eNOS and VEGF were measured in biopsy specimens from 25 patients with reflux esophagitis, using TaqMan PCR and reverse transcription PCR. RESULTS: The expression of iNOS mRNA in the esophageal mucosa increased parallel to the severity of the esophagitis. There were no significant differences between both eNOS and VEGF mRNA expression levels and the severity of the esophagitis. The existence of gastric mucosal atrophy, hiatus hernia, therapy and Helicobacter pylori infection did not affect the levels of mRNA expression. CONCLUSIONS: The accumulation of NO, produced by iNOS, was considered to be related to the exacerbation of reflux esophagitis. Therapeutic intervention that reduces NO production may thus be of use in preventing development of esophageal mucosal injury in patients with reflux esophagitis.

Pleural effusions following endoscopic injection sclerotherapy for cirrhotic patients with esophageal varices.

BACKGROUND/AIMS: Endoscopic injection sclerotherapy is in widespread use for patients with esophageal varices. It is well known that pleural effusions are among complications following endoscopic sclerotherapy. However, there are few studies regarding the proportion of patients developing pleural effusions after sclerotherapy. METHODOLOGY: Between August 1991 and September 1998, 575 endoscopic injection sclerotherapies were carried out in 128 patients. Chest radiographs were obtained prior to and 24 hours after all procedures. We also obtained other clinical data from all patients. RESULTS: In total, 17.7% of post-sclerotherapy patients were diagnosed as having small amounts of pleural effusions. Logistic regression revealed pleural effusions after sclerotherapy to be associated with ascites, chest pain for 24 hours, total volume of sclerosant and submucosal injection of more than 4mL of sclerosant. In parallel with injection of an increasing amount of submucosal sclerosant, the proportion of patients with pleural effusion increased. CONCLUSIONS: Pleural effusions were related to ascites, chest pain for 24 hours, total sclerosant volume and submucosal injection of sclerosant.

Clinical characteristics of Japanese reflux esophagitis patients as determined by Los Angeles classification.

BACKGROUND: Recent studies have shown that the number of patients with reflux esophagitis is increasing in Japan, but the prevalence and risk factors associated with reflux esophagitis in Japanese patients are not well defined. METHODS: By using all endoscopic records in the Katta General Hospital from April through to September 1999, we identified 392 patients. We examined the Los Angeles classification, peptic ulcer, gastric mucosal atrophy, hiatal hernia and other medical variable factors for their contribution to esophagitis in the patients. RESULTS: Patients (13.8%) were diagnosed as having reflux esophagitis with a mucosal break. In a multivariate analysis, reflux esophagitis was associated with hiatal hernia (odds ratio (OR) 2.276, 95% confidence interval (CI) 1.164-4.450), with patients over 65 years of age (OR 2.521, 95% CI 1.238-5.134) and the open type of gastric mucosal atrophy (OR 0.420, 95% CI 0.225-0.785). There was no significant difference between esophagitis and Helicobacter pylori infection and peptic ulcer. CONCLUSIONS: We observed that age, hiatal hernia and a lower rate of gastric mucosal atrophy were associated with the proportion of mucosal breaks accompanying esophagitis.