Yuko Izumi

Treatment of functional dyspepsia with antianxiety or antidepressive agents : systematic review

BackgroundThe pathophysiology of functional dyspepsia (FD) has not been elucidated precisely; accordingly, effective management of FD has not yet been found. Until now, treatment with antianxiety or antidepressive agents has been empirically applied; however, the efficacy of these treatments has not been established. We carried out this study to estimate the efficacy of these treatment approaches by systematically reviewing the literature concerning trials with agents that are efficacious against anxiety, neurosis, or depression.MethodsArticles were searched from the MEDLINE database up to October 2003, using the terms, “antianxiety agents”, “antidepressants”, and “dyspepsia”, and from reference lists of published articles. Finally, studies in which the effectiveness of drugs was clearly stated were selected from the retrieved articles.ResultsThirteen articles, on 1717 patients, were selected from among 90 articles retrieved through our literature search. In 11 of the 13 studies, dyspeptic symptoms were improved significantly by treatment. Statistical analysis of 4 trials showed a significant benefit of treatment with antianxiety or antidepressive agents (pooled relative risk, 0.55; 95% confidence interval [CI], 0.36–0.85), although funnel plots were asymmetric.ConclusionsAntianxiety or antidepressive agents may be effective in the treatment of FD patients, though further clinical trials are necessary.

Overexpression of a 60-kDa heat shock protein enhances cytoprotective function of small intestinal epithelial cells.

AIMS With the advancement of small intestinal (double balloon and capsule) endoscopy technology, incidence of small intestinal lesion caused by nonsteroidal anti-inflammatory drugs (NSAIDs) has been known to be high. However, therapy for small intestinal mucosal lesion has not yet been developed. Previous studies have shown that heat shock proteins (HSPs) are involved in cytoprotection mediated by their function as a molecular chaperone. In this study, we examined the effect of HSP60 or HSP70 overexpression on hydrogen peroxide-induced (H2O2) or indomethacin-induced cell damage in the small intestinal epithelial cells. MAIN METHODS cDNA of human HSP60 or HSP70 was transfected to rat small intestinal (IEC-6) cells, and HSP60- or HSP70-overexpressing cells were cloned. IEC-6 cells transfected with vector only were used as control cells. These cells were treated with H2O2 (0-0.14mM) or indomethacin (0-2.5mM). The cell viability was determined by MTT-assay. Cell necrosis was evaluated by LDH-release assay. Further, apoptosis was evaluated by caspases-3/7 activity and TUNEL assay. KEY FINDINGS Cell viability after H2O2 or indomethacin treatment was significantly higher in HSP60-overexpressing cells compared with that in control cells and HSP60-overexpressing cells. Apoptotic cells were also reduced in HSP60-overexpressing. CONCLUSION These results indicate that HSP60 plays an important role in protecting small intestinal mucosal cells from H2O2-induced or indomethacin-induced cell injury. HSP70-overexpressing cells did not show anti-apoptotic ability. SIGNIFICANCE These findings possibly suggest that function of each HSP is different in the small intestine. Therefore, for the therapy of small intestinal mucosal lesion, HSP60-induction therapy could be a new therapeutic strategy.

Juvenile hepatocellular carcinoma with congestive liver cirrhosis

A case of juvenile hepatocellular carcinoma (HCC) with congestive liver cirrhosis is reported. The patient was a 21-year-old woman. She had been diagnosed as having transposition of the great arteries, type 2, in 1978. She underwent the Mustard operation, but suffered from chronic heart failure. In 1995, she experienced abdominal pain and underwent examination. The laboratory data were normal, except for elevated total bilirubin (5.2 mg/dl). Blood examinations were performed at frequent intervals, and the total bilirubin level fluctuated between 0.9 and 8.1 mg/dl over the next 4 years, but the transaminase level remained normal. In 1999, she experienced abdominal pain again and was admitted to our hospital. Computed tomography showed four space-occupying lesions in the liver; 45 mm, 20 mm, 12 mm, and 10 mm in size. She was diagnosed as having HCC, and transcatheter arterial chemoembolization and percutaneous ethanol injection therapy were performed. Histology of the cancerous and the noncancerous liver tissue revealed HCC, moderately differentiated type, in cirrhotic liver with congestion. This patient had no background factors of liver disease, except for liver congestion, associated with the chronic heart failure. Because most patients with cardiac cirrhosis die of cardiac disease, only a small number of these patients develop liver failure. However, the incidence of HCC in patients with congestive liver disease is likely to increase in the future, as survival time is prolonged with the advances in treatment for chronic heart failure. Therefore, patients with congestive liver disease should be followed, taking into account the possibility of HCC.

Endoscopic retrieval of a gastric trichobezoar

A 9-year-old girl presented with a chief complaint of abdominal pain. Esophagogastroduodenal endoscopy (EGD) identified a long and large gastric trichobezoar extending into the duodenum. We attempted endoscopic retrieval after informed consent was obtained from the patients mother. Initially, a gasper with 5-prolongs, commonly used for retrieval of endoscopically excised polyps, failed to remove the whole trichobezoar. When a net was used instead, it proved impossible to remove the trichobezoar completely. Therefore, we withdrew the scope from the mouth, leaving the net grasping the tricobezoar firmly in the stomach. Subsequently, we were able to retrieve about 70% of the trichobezoar manually by grasping the snare part of the net directly. A second pass found no deep laceration or perforation endoscopically. The remaining trichobezoar was completely retrieved with the net. The procedure was completed within 15 min. The retrieved specimens were 34 cm in length and 100 g in weight. The patient was discharged uneventfully 5 d thereafter. She was advised to visit a psychiatrist to avoid suffering from a relapse. Follow-up EGD showed no trichobezoar, and the patients frontal hair grew back.

Target molecules of molecular chaperone (HSP70 family) in injured gastric mucosa in vivo

AIMS Several recent studies, including ours, have indicated the importance of heat shock proteins (HSPs) in cytoprotection against cytotoxic agents and environmental stresses mediated by the chaperone function of HSPs (molecular chaperones). However, the target molecule that is recognized by HSPs in damaged cells currently remains unknown. As HSPs rapidly recognize and bind to degenerated protein in cells, target molecules of HSPs might be key molecules for the initiation and pathogenesis of cellular damage. In the present study, gastric mucosal proteins that specifically bind to the HSP70 family (HSC70) were analyzed using HSC70-affinity chromatography. MAIN METHODS The gastric mucosa was removed from Sprague-Dawley rats after exposure to water immersion-stress for 0, 1, 3 or 5 h. Soluble fractions of each gastric mucosa were applied to the HSC70-affinity column separately. After washing off non-specific binding proteins, specific binding proteins were eluted by ATP-containing buffer. Binding proteins were analyzed by SDS-polyacrylamide gel electrophoresis. In addition, the amino acid sequence of purified proteins was also analyzed. KEY FINDINGS Specific HSC70-binding proteins with a molecular weight of 200-kDa and 45-kDa were eluted from an affinity column when gastric mucosal homogenate of 1-h stress exposure was applied. The amino acid sequencing showed that these binding proteins were cytoskeletal myosin (heavy chain) and actin, respectively. SIGNIFICANCE During the pathogenesis of stress-induced gastric mucosal damage, structurally degenerated cytoskeletal myosin (heavy chain) and actin may be key or initiation molecules which structural changes were firstly recognized by molecular chaperone.

A novel endoscopic ablation of gastric antral vascular ectasia

An 80-year-old woman was admitted to our hospital because of tarry stool with iron deficiency anemia. Her past history included autoimmune hepatitis. Esophagogastroduodenal endoscopy was performed to investigate the bleeding source and revealed multiple linear gastric vascular malformations in the antrum and cardia, compatible with Gastric antral vascular ectasia (GAVE). Endoscopic ablation was carried out with the tip of the hot biopsy forceps without opening at soft coagulation mode of 80W. The patient tolerated the procedure well and there were no complications associated with endoscopic therapies. After two sessions of endoscopic ablation her anemia improved to around 10 g/dL, an increase of 3.6 g/dL. Various endoscopic treatments have been described to manage GAVE. The most popular is argon plasma coagulation (APC), although APC is associated with over-distension induced by the argon plasma gas. To avoid over-distension and to reduce the abdominal discomfort/pain of this patient, we have used hot biopsy forceps instead of APC. Our case suggests that this procedure is effective, easy and convenient, as no special equipment or skill is necessary.

Specific induction of a 72-kDa heat shock protein protects esophageal mucosa from reflux esophagitis

AIMS The aim of this study is to investigate the expression and cytoprotective function of a 72-kDa heat shock protein (HSP72) using a reflux esophagitis model in rats. MAIN METHODS Expression of HSP60, HSP72, and HSP90 in rat esophageal mucosa was evaluated by Western blot analysis before and after hyperthermia (42.5 degrees C, 20 min). Rats received the operation to produce reflux esophagitis with or without pretreatment with hyperthermia to induce HSPs. The esophageal mucosal damage was evaluated 12 h after the operation. KEY FINDINGS Expression of HSP72 was significantly increased by hyperthermia in rat esophageal mucosa. Reflux esophagitis was dramatically prevented when HSP72 was preinduced by hyperthermia. Furthermore, activation of TNF-alpha and IL-1beta in esophageal mucosa was also suppressed. SIGNIFICANCE These results suggested that hyperthermia protects the esophageal mucosa in reflux esophagitis model by inducing HSP72 and suppressing proinflammatory cytokine activation. These findings might suggest that HSP-inducing therapy could be a novel and unique therapy for reflux esophagitis.

Correlation of Heat Shock Protein Expression to Gender Difference in Development of Stress-Induced Gastric Mucosal Injury in Rats

Recent studies have indicated that heat shock proteins (HSPs), which function as molecular chaperones, play important roles in cellular responses to stress-related events. However, the gender difference in the expression of HSP in the gastric mucosa remains unclear. In order to understand the mechanism of gender difference in the prevalence or severity of gastric mucosal lesions, the expression level of HSP and the correlation of estrogen to HSP induction in the gastric mucosa were evaluated in this study. The basal expression levels of HSP60 and HSP90 in the gastric mucosa were significantly higher in females than those in males. The gastric ulcer index was significantly higher in male rats compared to female rats observed after 12 h water immersion stress exposure. At this time point, the expression levels of HSP60 and HSP90 in the gastric mucosa were significantly higher in females than those in males. An estrogen-treatment significantly induced the expression of HSP60, HSP70 and HSP90 in the gastric mucosa. Inversely, an ovariectomy dramatically reduced the expression of HSP60, HSP70 and HSP90 in the gastric mucosa. Our results suggested that estrogen might play an important role in gastric mucosal protection with the induction of gastric mucosal HSPs.

T1702 Cytokines Regulate Tight-Junction Structure and Function in the Rat Chronic Acid Esophagitis Model

tomy had more frequently erosive esophagitis than patients with cholecystectomy (p<0.05). Conclusions: Colecystectomy do not increase the overall number of reflux episodes compared to patients without colecystectomy, but modifies significantly the composition of the refluxate raising the frequency of nonacid reflux. The different proportion of acid/nonacid reflux may explain the higher presence of erosive esophagitis in nCCE patients.

W1066 Estblishment of Rats Reflux Laryngitis Model

Gastroesophageal reflux (GER) and aspiration of gastric components has been implicated in the pathophysiology of ENT and chronic respiratory diseases. We previously demonstrated that patients with chronic cough, LTx and cystic fibrosis may have both, acid and non-acid reflux. Furthermore, non acid gastric juice from patients “on” PPI is able to trigger increased inflammatory reaction from human bronchial epithelial cells in culture. Animal experiments showed that only acid and bile acids in acidic environment were able to provoke damage in laryngeal mucosa. Patients “on” PPI treatment have persistent reflux of gastric contents with high pH, bile acids and increased bacterial subproducts (LPS). The role of this type of refluxate in extraesophageal GERD is still controversial. The aim of this study was to evaluate the effect of non acidic solutions with or without gastro-duodenal contents and LPS on functional tracheal mucosal integrity.Methods:New Zealand rabbits were euthanized and tracheal segments were mounted in Ussing Chambers for assessment of transepithelial mucosal resistance (TER). Substance P release (a neurotransmitter and marker of mucosal injury) was measured at the mucosal side. Tracheal mucosa was exposed for 20 min to a control solution (Krebs pH 7.4) or to test solutions containing deoxycholic acid (DC, 0.52mM), pepsin (0.4-1 mg/ml) or endotoxin (LPS) (1 g/ml). Results: Exposure of the tracheal mucosa to acidic solutions (pH 1.2, 1.5 and 2), without gastric components, induced a significant drop in TER of 82, 73 and 55% respectively (N=4). Less acidic solutions (pH 34) did not have an effect on the integrity of the tissue. However incubating the tissue with DC (0.5-2mM) at weakly acidic pH (pH 3-4) significantly reduced TER (by 34-30 %), whereas pepsin (0.4-1 mg/ml) was not able to provoke changes in TER at pH > 3 (N=4). Neutral solutions (pH 7.4) with DC (1.5mM) or pepsin (1 mg/ml) did not increase SP. However, exposure to LPS (1 μg/ml, pH 7.4) significantly increased SP release compared to control. Conclusions: Not only acidic solutions but also weakly acidic solutions (pH 34) containing bile acids can harm the functional integrity of the tracheal mucosa In Vitro. Local SP release, induced by endotoxins present in gastro-duodenal refluxate of patients “on” PPI, may further promote an inflammatory reaction.