Association between metabolic syndrome and prevalence of gastroesophageal reflux disease in a health screening facility in Japan.

BACKGROUND: Abdominal fat accumulation, which induces high intra-abdominal pressure that causes increase in the gastroesophageal pressure gradient and hiatal hernia, as well as obesity, has been shown to increase the prevalence of gastroesophageal reflux disease (GERD). This study was performed to clarify the association between metabolic syndrome and the prevalence of GERD. METHODS: The study subjects were an adult population who visited a medical center for annual medical check-ups from April 2010 to March 2011. GERD was diagnosed by the presence of endoscopically proven reflux esophagitis, GERD symptoms (QUEST score ≥6), or current medical therapy for GERD. The presence of metabolic or pre-metabolic syndrome was diagnosed based on the Japanese criteria for metabolic syndrome. RESULTS: Six hundred four (16.0 %) of 3775 study subjects were positively diagnosed with GERD, with the number of those with metabolic and pre-metabolic syndrome being 477 (12.6 %) and 384 (10.2 %), respectively. Multiple logistic regression analysis showed that male gender, presence of hiatal hernia, and metabolic or pre-metabolic syndrome, as well as absence of gastric mucosal atrophy, were significant predictive factors for the prevalence of GERD, as were visceral fat accumulation and untreated dyslipidemia. Untreated hypertension and untreated hyperglycemia were also considered to be positive risk factors. Subjects undergoing treatment for hypertension showed an increased risk of GERD, while those undergoing treatment for dyslipidemia and diabetes mellitus showed a decreased risk. CONCLUSION: Metabolic syndrome is a reliable predictive factor for the prevalence of GERD, and medical therapy for metabolic syndrome may modify the risk of GERD occurrence.

Role of C-terminal negative charges and tyrosine residues in fibril formation of α-synuclein.

α-Synuclein (140 amino acids), one of the causative proteins of Parkinson's disease, forms amyloid fibrils in brain neuronal cells. In order to further explore the contributions of the C-terminal region of α-synuclein in fibril formation and also to understand the overall mechanism of fibril formation, we reduced the number of negatively charged residues in the C-terminal region using mutagenesis. Mutants with negative charges deleted displayed accelerated fibril formation compared with wild-type α-synuclein, demonstrating that negative charges located in the C-terminal region of α-synuclein modulate fibril formation. Additionally, when tyrosine residues located at position 125, 133, and 136 in the C-terminal region were changed to alanine residue(s), we found that all mutants containing the Tyr136Ala mutation showed delays in fibril formation compared with wild type. Mutation of Tyr136 to various amino acids revealed that aromatic residues located at this position act favorably toward fibril formation. In mutants where charge neutralization and tyrosine substitution were combined, we found that these two factors influence fibril formation in complex fashion. These findings highlight the importance of negative charges and aromatic side chains in the C-terminal region of α-synuclein in fibril formation.

Comparative study of nizatidine and famotidine for maintenance therapy of erosive esophagitis.

BACKGROUND: The therapeutic effect of combined administration of prokinetics and histamine H2 receptor antagonists (H2RA) in gastroesophageal reflux disease is reported to be superior to that of monotherapy with H2RA alone. In addition to its acid-suppressing effect, the H2RA nizatidine also has a prokinetic action by suppressing acetylcholine esterase. The present multicenter, randomized controlled study was performed to investigate whether nizatidine is superior to famotidine, which does not suppress acetylcholine esterase activity, in maintenance therapy for erosive esophagitis. In addition, the question as to whether the grade of erosive esophagitis affects the non-recurrence rate during the maintenance therapy with H2RA was also investigated. METHODS: Seventy-two patients with endoscopically healed erosive esophagitis after 8 weeks of initial treatment with proton pump inhibitors were randomly divided into two groups. Patients in the nizatidine group were treated with 150 mg nizatidine twice a day (b.i.d.), while patients in the famotidine group were treated with 20 mg famotidine b.i.d. for 6 months. At the end of therapy, and at the time when patients complained of symptoms, endoscopic investigations were repeated to find out whether the esophagitis had recurred. RESULTS: Nizatidine produced a significantly higher non-recurrence rate than famotidine (P = 0.049 in intention-to-treat [ITT] analysis). This difference of remission rate between nizatidine and famotidine was observed mainly in grade B esophagitis (P = 0.016 in ITT analysis). CONCLUSION: Nizatidine is a more effective H2RA than famotidine in the maintenance therapy of patients with reflux esophagitis.

Symptom relief in patients with reflux esophagitis: comparative study of omeprazole, lansoprazole, and rabeprazole.

BACKGROUND AND AIM: Rabeprazole has a faster onset of antisecretory activity than omeprazole and lansoprazole. The aim of the present study was to clarify whether there is any difference in the speed of symptom relief in patients with reflux esophagitis following the administration of these three proton pump inhibitors (PPI). METHODS: Eighty-five patients with erosive reflux esophagitis were randomized to receive 8 weeks of 20 mg of omeprazole (n = 30), 30 mg of lansoprazole (n = 25), or 20 mg of rabeprazole (n = 30) once a morning. Daily changes in heartburn and acid reflux symptoms in the first 7 days of administration were assessed using a six-point scale (0: none, 1: mild, 2: mild-moderate, 3: moderate, 4: moderate-severe, 5: severe). RESULTS: The mean heartburn score in patients administered rabeprazole decreased more rapidly than those given the other PPI. Complete heartburn remission also occurred more rapidly in patients administered rabeprazole (compared with omeprazole: P = 0.035, compared with lansoprazole: P = 0.038 by log-rank test). No differences were seen in the rate of endoscopic healing of reflux esophagitis at 8 weeks between the three treatment regimens. CONCLUSION: Rabeprazole may be more effective than omeprazole and lansoprazole for the rapid relief of heartburn symptoms in patients with reflux esophagitis.