The therapeutic effects of the peptidyl-prolyl cis/trans isomerase Pin1 inhibitor juglone on animal-model experimental autoimmune encephalomyelitis.

Multiple sclerosis (MS) is a chronic inflammatory demyelinating disease of the central nervous system (CNS). There is currently no satisfactory treatment for this disease. Pin1 is the only known peptidyl-prolyl cis/trans isomerase (PPIase) that is involved in many cellular processes, including immune responses. Numerous studies have shown that juglone effectively inhibits Pin1 activity. However, the effect of Pin1 inhibitor juglone on autoimmune diseases such as multiple sclerosis (MS) and its animal model, experimental autoimmune encephalomyelitis (EAE), remain incomplete. So the present study aimed to explore the therapeutic effects of the Pin1 inhibitor juglone on EAE. EAE was induced in C57BL/6 mice with myelin oligodendrocyte glycoprotein (MOG)35-55 and treatment with juglone. The health status of EAE was observed and inflammation explored using pathological analysis. The impact of juglone on immune cells was further examined using intracellular staining and flow cytometry. The results demonstrated that juglone ameliorates EAE and reduces inflammation and demyelination in the CNS. The study also found that juglone suppresses pathogenic Th1 and Th17 cells and the expression of CD83 and MHCII on dendritic cells in EAE. In addition, juglone ameliorates EAE. Pin1 inhibitors therefore hold great promise for autoimmune disease and MS therapy.

Application of magnifying endoscopy with narrow-band imaging in diagnosing gastric lesions: a prospective study.

BACKGROUND: Magnifying endoscopy with narrow-band imaging (ME-NBI) can more clearly assess the surface pattern and microvascular architecture of gastric lesions. OBJECTIVE: To evaluate the diagnostic efficacy of ME-NBI in patients with early gastric cancer. DESIGN: Prospective study. SETTING: Single academic center. PATIENTS: This study involved 164 suspected gastric lesions in 146 consecutive patients who underwent ME-NBI for additional differential diagnosis before treatment. INTERVENTION: ME-NBI findings were classified into 3 groups based on irregularities, absence of surface pattern, and microvascular architecture. All lesions were treated endoscopically or surgically, and ME-NBI diagnosis was compared with histopathological findings. MAIN OUTCOME MEASUREMENTS: Sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of real-time ME-NBI diagnosis were determined. RESULTS: The sensitivity, specificity, and accuracy of ME-NBI were 97.3%, 84.4%, and 90.2%, respectively, in distinguishing between cancerous and noncancerous lesions and were 92.3%, 89.7%, and 90.4%, respectively, in distinguishing undifferentiated from differentiated adenocarcinoma. ME-NBI accurately predicted depth of invasion in 37 of 39 differentiated adenocarcinomas (95%). LIMITATIONS: The sample size was relatively small. CONCLUSIONS: ME-NBI can successfully distinguish between cancerous and noncancerous lesions and between undifferentiated and differentiated adenocarcinomas. Of the 3 patterns on ME-NBI, type A is mainly characteristic of noncancerous lesions, type B is a good indicator of differentiated adenocarcinoma and intramucosal/superficially invasive cancers, and type C is indicative of undifferentiated adenocarcinoma or differentiated cancer with deep submucosal invasion.

A pilot study of endoscopic spray cryotherapy by pressurized carbon dioxide gas for Barrett's esophagus.

BACKGROUND AND STUDY AIMS: Endoscopic spray cryoablation is a novel approach for the treatment of Barrett's esophagus. However, few studies have reported its efficacy, especially with the use of carbon dioxide (CO (2)). The aim of the current study was to evaluate the short term efficacy and complications using CO (2) in endoscopic cryoablation of Barrett's esophagus. METHODS: Patients diagnosed with Barrett's esophagus underwent monthly stepwise cryoablation with pressurized CO (2) gas, with follow-up esophageal biopsies until complete histological reversal was achieved. Responses were analyzed with an intention-to-treat analysis according to complete response for intestinal metaplasia (CR-IM), which was defined as the elimination of all intestinal metaplasia including specialized intestinal metaplasia (SIM), subsquamous SIM, and dysplasia with intestinal metaplasia in the biopsies under narrow-band imaging (NBI). RESULTS: In total, 22 patients were enrolled, 20 of whom completed the treatment. Two patients declined further ablation after the first cryotherapy session. A total of 44 sessions were performed; a median of 2 sessions per patient (range 1 - 3 sessions) were needed to complete the ablation of Barrett's esophagus. No severe complications occurred. Follow-up endoscopies were performed in 20 patients (90.9 %). Two patients (9.1 %) were lost to follow-up. Median follow-up was 10 months (range 6 - 18 months). After cryotherapy, 20 patients (90.9 %) reached CR-IM of Barrett's esophagus. Patients underwent a median number of 3 follow-up endoscopies (range 2 - 4) with biopsies. At 6 months, recurrence was evident in three patients (13.6 % of the overall population, 15.0 % of the CR-IM population). One of the three patients developed intestinal metaplasia but no dysplastic change and the other two developed subsquamous SIM. CONCLUSIONS: The pressurized CO (2) spray cryotherapy is a relatively effective and safe endoscopic treatment for Barrett's esophagus.

Duodenal gastric metaplasia and Helicobacter pylori infection in patients with diffuse nodular duodenitis.

Whether the regression of gastric metaplasia in the duodenum can be achieved after eradication of Helicobacter pylori is not clear. The aim of the present study was to investigate the relationship between H. pylori infection and gastric metaplasia in patients with endoscopic diffuse nodular duodenitis. Eighty-six patients with endoscopically confirmed nodular duodenitis and 40 control patients with normal duodenal appearance were investigated. The H. pylori-positive patients with duodenitis received anti-H. pylori triple therapy (20 mg omeprazole plus 250 mg clarithromycin and 400 mg metronidazole, all twice daily) for one week. A control endoscopy was performed 6 months after H. pylori treatment. The H. pylori-negative patients with duodenitis received 20 mg omeprazole once daily for 6 months and a control endoscopy was performed 2 weeks after treatment. The prevalence of H. pylori infection was 58.1%, and the prevalence of gastric metaplasia was 57.0%. Seventy-six patients underwent endoscopy again. No influence on the endoscopic appearance of nodular duodenitis was found after eradication of H. pylori or acid suppression therapy. However, gastric metaplasia significantly decreased and complete regression was achieved in 15/28 patients (53.6%) 6 months after eradication of H. pylori, accompanied by significant improvement of other histological alterations. Only mild chronic inflammation, but not gastric metaplasia, was found in the control group, none with H. pylori infection in the duodenal bulb. Therefore, H. pylori infection is related to the extent of gastric metaplasia in the duodenum, but not to the presence of diffuse nodular duodenitis.

Duodenal gastric metaplasia and Helicobacter pylori infection in patients with diffuse nodular duodenitis

Whether the regression of gastric metaplasia in the duodenum can be achieved after eradication of Helicobacter pylori is not clear. The aim of the present study was to investigate the relationship between H. pylori infection and gastric metaplasia in patients with endoscopic diffuse nodular duodenitis. Eighty-six patients with endoscopically confirmed nodular duodenitis and 40 control patients with normal duodenal appearance were investigated. The H. pylori-positive patients with duodenitis received anti-H. pylori triple therapy (20 mg omeprazole plus 250 mg clarithromycin and 400 mg metronidazole, all twice daily) for one week. A control endoscopy was performed 6 months after H. pylori treatment. The H. pylori-negative patients with duodenitis received 20 mg omeprazole once daily for 6 months and a control endoscopy was performed 2 weeks after treatment. The prevalence of H. pylori infection was 58.1 percent, and the prevalence of gastric metaplasia was 57.0 percent. Seventy-six patients underwent endoscopy again. No influence on the endoscopic appearance of nodular duodenitis was found after eradication of H. pylori or acid suppression therapy. However, gastric metaplasia significantly decreased and complete regression was achieved in 15/28 patients (53.6 percent) 6 months after eradication of H. pylori, accompanied by significant improvement of other histological alterations. Only mild chronic inflammation, but not gastric metaplasia, was found in the control group, none with H. pylori infection in the duodenal bulb. Therefore, H. pylori infection is related to the extent of gastric metaplasia in the duodenum, but not to the presence of diffuse nodular duodenitis.

The role of simeticone in small-bowel preparation for capsule endoscopy.

BACKGROUND AND STUDY AIMS: Capsule endoscopy is a new diagnostic method allowing painless visualization of the entire small bowel. However, there is as yet no standardized protocol for bowel preparation before the examination. The aim of this study was to assess the effectiveness of simeticone in reducing bowel gas bubbles in patients undergoing capsule endoscopy. PATIENTS AND METHODS: A randomized, prospective, and controlled study was conducted, including 56 patients, from March to October 2004. The patients were randomly allocated to groups receiving either simeticone or no simeticone, on the basis of a computer-generated random number table. Patients in the simeticone group (n = 28) received 300 mg simeticone for bowel preparation 20 min before capsule endoscopy, while patients in the non-simeticone group (n = 28) received no medication for bowel preparation. Two experienced endoscopists assessed and graded the visibility of the mucosa and intraluminal gas bubbles in a single-blinded fashion. RESULTS: The visibility of the mucosa in the proximal small bowel in patients who received preparation with simeticone was considered to be better, with fewer intraluminal bubbles, than in those without bowel preparation ( P < 0.025). Interobserver agreement was excellent ( R > or = 0.8, P < 0.05). No adverse effects of simeticone were observed. CONCLUSIONS: Simeticone administration before capsule endoscopy improves the visualization of the mucosa in the proximal small intestine.

Clinical trial of gabexate in the prophylaxis of post-endoscopic retrograde cholangiopancreatography pancreatitis.

The objective of the present study was to determine the efficacy of prophylactic administration of gabexate for the prevention of post-endoscopic retrograde cholangiopancreatography (ERCP) pancreatitis, hyperamylasemia and pancreatic pain. Patients scheduled for ERCP were randomized into two groups in a double-blind manner: the patients in the gabexate group were treated with continuous intravenous infusion of 300 mg gabexate dissolved in 500 mL Ringer's solution at 111 mL/h, starting 30 min before the endoscopic maneuvers and continuing up to 4 h after them; placebo group patients were treated only with Ringer's solution also starting 30 min before the endoscopic maneuvers and continuing up to 4 h. Data for 193 patients were analyzed. The incidence of post-ERCP pancreatitis was 3 patients (3.1%) in the gabexate group and 10 (10.5%) in the placebo group (P = 0.040). The incidence of hyperamylasemia was 33 patients (33.7%) in the gabexate group and 42 (43.7%) in the placebo group (P = 0.133). The incidence of pancreatic pain was 15 patients (15.3%) in the gabexate group and 28 (29.5%) in the placebo group (P = 0.018). The results suggest that a 4.5-h infusion of gabexate (for a total of 300 mg) could prevent post-ERCP pancreatitis and pancreatic pain.

Clinical trial of gabexate in the prophylaxis of post-endoscopic retrograde cholangiopancreatography pancreatitis

The objective of the present study was to determine the efficacy of prophylactic administration of gabexate for the prevention of post-endoscopic retrograde cholangiopancreatography (ERCP) pancreatitis, hyperamylasemia and pancreatic pain. Patients scheduled for ERCP were randomized into two groups in a double-blind manner: the patients in the gabexate group were treated with continuous intravenous infusion of 300 mg gabexate dissolved in 500 mL Ringer's solution at 111 mL/h, starting 30 min before the endoscopic maneuvers and continuing up to 4 h after them; placebo group patients were treated only with Ringer's solution also starting 30 min before the endoscopic maneuvers and continuing up to 4 h. Data for 193 patients were analyzed. The incidence of post-ERCP pancreatitis was 3 patients (3.1 percent) in the gabexate group and 10 (10.5 percent) in the placebo group (P = 0.040). The incidence of hyperamylasemia was 33 patients (33.7 percent) in the gabexate group and 42 (43.7 percent) in the placebo group (P = 0.133). The incidence of pancreatic pain was 15 patients (15.3 percent) in the gabexate group and 28 (29.5 percent) in the placebo group (P = 0.018). The results suggest that a 4.5-h infusion of gabexate (for a total of 300 mg) could prevent post-ERCP pancreatitis and pancreatic pain.

Does eradication of Helicobacter pylori alone heal duodenal ulcers?

BACKGROUND: Eradication of Helicobacter pylori infection prevents duodenal ulcer (DU) relapse, but it remains uncertain whether eradication of H. pylori alone heals duodenal ulceration. AIM: To test the hypothesis that eradication of H. pylori infection is accompanied by healing of duodenal ulcer. METHODS: A total of 115 consecutive patients with endoscopically confirmed H. pylori-infected duodenal ulcer were randomly assigned to one of two groups. Group BTC patients received a 1-week course of colloidal bismuth subcitrate 220 mg b.d., tinidazole 500 mg b.d., clarithromycin 250 mg b.d. Group OBTC patients received omeprazole 20 mg daily for 4 weeks with the BTC regimen during the first week. Endoscopy with antral biopsies and 13C-urea breath test (UBT) were performed before and 4 weeks after completion of the 7-day triple or quadruple therapy. RESULTS: Eight patients dropped out (four in BTC and four in OBTC). Duodenal ulcer healing rates on an intention-to-treat basis in BTC and OBTC were 86% (95% CI: 77-95%) and 90% (95% CI: 82-98%), respectively. The eradication rates of H. pylori on an intention-to-treat basis in BTC and OBTC were 88% (95% CI: 79-96%) and 91% (95% CI: 84-99%), respectively. There were no statistically significant differences in ulcer healing rates and eradication rates between these two groups (P > 0.05). Epigastric pain resolved more rapidly in patients assigned to OBTC compared with those assigned to BTC. Both of the two regimens were well tolerated with only minor side-effects (3% of the 115 patients) and the compliance was good. CONCLUSIONS: BTC is a very effective H. pylori eradication regimen. Almost all duodenal ulcers heal spontaneously after cure of H. pylori infection using a 1-week low-dose bismuth-based triple therapy. Treating duodenal ulcer with simultaneous administration of omeprazole achieves ulcer pain relief more rapidly.