Biomedical subjects

Akira Andoh

Publications and source records attributed to Akira Andoh.

81 records · Page 5Linked to original sources

PubMed2002

Suppressive effects of a new anti-inflammatory agent, IS-741, on dextran sulfate sodium-induced experimental colitis in rats.

A novel anti-inflammatory drug, IS-741, blocked the adhesion of inflammatory cells to microvascular endothelial cells in vivo and in vitro. We examined the efficacy of IS-741 in a dextran sulfate sodium (DSS)-induced colitis model. DSS colitis was induced by the oral administration of 3% DSS for 10 days in rats. The rats were then divided in two groups: a 1% DSS plus IS-741 group and a 1% DSS plus water group. IS-741 was dissolved in water and administered orally (10 mg/kg) once per day for 14 days. The rats treated with DSS plus IS-741 remained healthy, and their body weight increased. The wet weight of the colon was significantly lower and the total colon length was significantly longer in the IS-741-treated group. Histological examinations revealed a marked infiltration of inflammatory cells into both the mucosa and submucosa in the DSS plus water group, but these changes were attenuated in the IS-741-treated group. The mucosal damage score was significantly reduced by treatment with IS-741. IS-741 also significantly reduced the mucosal myeloperoxidase activity. FACS analysis revealed that IS-741 significantly reduced Mac-1 expression on blood neutrophils. In conclusion, IS-741 suppressed DSS-induced experimental colitis in rats. Some of the action of IS-741 may be associated with its inhibitory effects on the Mac-1 expression of neutrophils in association with the blockade of their adhesion to endothelial cells. The findings in this study suggest that IS-741 may be a useful new therapeutic agent for inflammatory bowel disease.

Animals↗

PubMed2002

Elevated serum anti-carbonic anhydrase II antibodies in patients with ulcerative colitis.

An autoimmune mechanism has been postulated for the pathogenesis of ulcerative colitis (UC). The aim of this study was to evaluate the presence of anti-carbonic anhydrase (CA) I and anti-CA II antibodies in a series of inflammatory bowel disease (IBD) patients. We studied 58 IBD patients [36 UC patients and 21 patients with Crohn's disease (CD)]. As a control, 24 healthy individuals and 12 patients with non-IBD diarrheal diseases were tested. Serum anti-CA I and anti-CA II antibodies were quantified by enzyme-linked immunosorbent assay. Anti-CA II antibody was detected in 27.8% of UC patients, whereas anti-CA I antibody was detected in only 5.6% of UC patients. Positive rate of anti-CA II antibody was significantly higher in UC patients as compared to the control. In CD patients and non-IBD diarrheal patients, there were no significant increase in positive rate of either anti-CA I or II antibody. These results suggest that autoimmune responses against CA II may be involved in the pathogenesis of UC, and similar mechanism may participate in the development of pancreatic lesions in UC patients.

Adult↗

PubMed2002

In vitro alterations in fecal short chain fatty acids and organic anions induced by the destruction of intestinal microflora under hypotonic and aerobic conditions.

The pathogenesis of inflammatory bowel disease (IBD) remains unknown. It has been suggested that luminal factors such as the microflora, short chain fatty acids (SCFAs), food antigens and so on play important roles in the disease progression. Many reports have revealed alterations in the SCFA and organic acid concentration of the colon, especially increased lactate and decreased butyrate, in IBD patients. The mechanisms responsible for these alterations, however, remain unclear. Therefore, the effects of aerobic conditions on the alterations in the SCFA and organic anion levels in the feces was evaluated. Fecal specimens were collected from 5 healthy volunteers. Under aerobic condition, a mixture of feces and distilled water was incubated in 37 degrees C for 1 and 3 h. The pH, osmotic pressures, the concentrations of potassium, bicarbonate, SCFA and organic anion, and the activities of alpha-amylase and lactate dehydrogenase (LDH) in the mixture were then measured. We also examined any changes in the microscopic microflora under the hypotonic and aerobic conditions. The results showed the osmotic pressure, and the concentrations of lactate and SCFAs (formate, acetate, propionate and n-valerate) were progressively increased with longer incubation times, and reached a statistically significant difference. In particular, the ratios of lactate, succinate and n-valerate after 1 and 3 h of incubation increased remarkably. In contrast, the electrolyte levels and both alpha-amylase and LDH activities were not altered significantly. Microscopically, the microflora in the mixture decreased with prolonged incubation times. These data suggest that under these in vitro conditions, the organic anion and SCFA levels in the feces easily increased. It is probable that the alterations in the SCFA and organic anion levels in IBD patients may be partly due to intracellular components derived from microflora destroyed under hypotonic and aerobic conditions in the colonic lumen, for example caused by mucosal bleeding. These alterations may influence the pathogenesis and progression of IBD.

Adult↗

PubMed2002

Inhibitory effects of somatostatin on tumor necrosis factor-alpha-induced interleukin-6 secretion in human pancreatic periacinar myofibroblasts.

Pancreatic periacinar myofibroblasts are considered to be therapeutic targets for the suppression of acute pancreatitis. To elucidate the mechanisms mediating the therapeutic actions of somatostatin on acute pancreatitis, we investigated how somatostatin affects the tumor necrosis factor (TNF)-alpha-induced interleukin (IL)-6 and IL-8 secretion from pancreatic myofibroblasts. Cytokine secretion was determined by enzyme-linked immunosorbent assay (ELISA) and Northern blotting. Nuclear factor (NF)-kappaB DNA-binding activity was evaluated by electrophoretic mobility shift assay (EMSAs). The expression of somatostatin receptor (SSTR) mRNA was evaluated by reverse transcription-polymerase chain reaction (RT-PCR). Somatostatin dose-dependently inhibited the TNF-alpha-induced IL-6 secretion. In comparison, the effects on IL-8 secretion were modest. Northern blot analysis demonstrated that somatostatin decreased the TNF-alpha-induced IL-6 mRNA expression, and that this effect was completely blocked by the somatostatin antagonist cyclo-somatostatin. Furthermore, somatostatin suppressed TNF-alpha-induced NF-kappaB activation. These cells bear SSTR subtypes 1 and 2. Somatostatin down-regulated the TNF-alpha-induced IL-6 secretion in human pancreatic periacinar myofibroblasts. These findings suggest that some of the therapeutic actions of somatostatin on acute pancreatitis might be mediated by reducing local IL-6 secretion in the pancreas.

Acute Disease↗

PubMed2002

Dietary bile acids inhibit potentially elemental diet-induced small intestinal atrophy in rats.

The mechanism responsible for elemental diet (ED)-induced small intestinal atrophy is still unknown. However, it is possible that bile acids in the gut lumen influence this process. The aim of this study was to evaluate the effects of oral bile acid administration during ED feeding. Specific pathogen-free male Sprague-Dawley rats, 10 weeks old, were fed an ED only, ED plus 0.1% (w/w) hyocholic acid, or ED plus 0.1% (w/w) hyodeoxycholic acid ad libitum for 4 weeks. The control rats were fed standard chow ad libitum for 4 weeks. After 4 weeks, the wet weight and whole length of the small intestine, and the mucosal diamine oxidase (DAO) and alkaline phosphatase (ALP) activities were measured. Microscopic histological observation was also performed. ED feeding induced atrophy and elevations in the mucosal DAO and ALP activities in the small intestine. Hyocholic acid and hyodeoxycholic acid administration both tended to inhibit these alterations. In conclusion, ED feeding induced atrophy and elevations in the mucosal DAO and ALP activities in the small intestine. Oral bile acid administration may prevent this atrophy and the elevations in mucosal DAO and ALP activities, which may lead to new therapeutic strategies in patients managed with ED.

Administration, Oral↗

PubMed2002

Interleukin (IL)-4 and IL-17 synergistically stimulate IL-6 secretion in human colonic myofibroblasts.

There is increasing evidence that interleukin (IL)-4 can aid in Th1-type inflammatory responses in chronic colitis models. In this study, we evaluated the effects of IL-4 and/or IL-17 on IL-6 secretion in human colonic myofibroblasts. IL-6 secretion was determined by ELISA and Northern blotting. IL-6 secretion was rapidly induced by either IL-4 or IL-17. IL-17 induced IL-6 mRNA expression within 1 h after stimulation, and reached a maximum at 3 h. IL-6 mRNA induction by IL-4 occurred more rapidly. A maximum induction of IL-6 mRNA by IL-4 was observed at 1 h after stimulation, and this was rapidly decreased. The combination of IL-4 plus IL-17 greatly enhanced IL-6 secretion and mRNA expression. In conclusion, IL-4, in particular IL-4 plus IL-17, induced IL-6 secretion in human colonic myofibroblasts. Th2 immune responses might play an important role in the pathogenesis of gut inflammation.

Cells, Cultured↗

PubMed2001

Sodium butyrate enhances complement-mediated cell injury via down-regulation of decay-accelerating factor expression in colonic cancer cells.

Decay-accelerating factor (DAF) expressed on the surface of colonic cancer cells presents a barrier to complement-mediated clearance by contributing to the ineffectiveness of the humoral immune response. In this study, to investigate the mechanisms responsible for the anti-tumor effects of butyrate, we evaluated how butyrate modulates DAF expression in colonic cancer cells. Three colonic cancer cell lines (HT-29, Caco-2, and T84 cells) were studied. DAF protein expression was assessed by western blot, and DAF mRNA expression was evaluated by northern blot. Complement C3 deposition on the surface of colonic cancer cells was determined by enzyme-linked immunosorbent assay (ELISA). The promoter activity of the DAF gene was assessed by a reporter gene-luciferase assay. Butyrate reduced the basal and interleukin-4 (IL-4)- and tumor necrosis factor-alpha (TNF-alpha)-induced expression of DAF protein and mRNA in HT-29 cells. It increased the susceptibility to complement attack and enhanced C3 deposition on HT-29 cells. The inhibitory effect of butyrate on DAF mRNA expression was also observed in T84 and Caco-2 cells. Butyrate decreased basal DAF expression at both transcriptional and post-transcriptional levels. The inhibitory effect of butyrate on IL-4-induced DAF expression was closely associated with a blockade of IL-4-induced DAF mRNA stability. TNF-alpha-induced transcriptional activation and the increased stability of the DAF gene were also blocked by butyrate. Similar but weak effects were induced by trichostatin A, a potent histone deacetylase inhibitor, suggesting that histone acetylation might participate in butyrate activity. These observations indicate that both a down-regulation of DAF expression and the induction of susceptibility to complement attack contribute to the anti-tumor effects of butyrate in colonic cancer.

Antineoplastic Agents↗

PubMedDate not supplied

The cytotoxicity of hydrophobic bile acids is ameliorated by more hydrophilic bile acids in intestinal cell lines IEC-6 and Caco-2.

Bile acids, especially those with hydrophobic properties, are known to possess cytotoxicity. However, the mechanisms responsible for the cytotoxicity of bile acids are still under investigation. On the other hand, the hydrophilic bile acid, ursodeoxycholic acid has been reported to exhibit therapeutic effects against cytotoxic hydrophobic bile acids. The aim of the present study was to investigate the cytotoxicity of individual bile acids and combinations of bile acids using the intestinal cell lines IEC-6 and Caco-2 cells. The cytotoxicities of individual bile acids and the effects of various bile acid combinations were evaluated using the MTS [3-(4, 5-dimethylthiazol-2-yl)-5-(3-carboxymethoxy-phenyl)-2-(4-sulfophenyl)-2H-tetrazolium] assay. The bile acids induced cytotoxic effects depending on their hydrophobicity except for hyodeoxycholic acid. In the study for the effects of combined bile acids, not only ursodeoxycholic acid but other hydrophilic bile salts such as cholic acid and hyocholic acid exhibited cytoprotection against deoxycholic acid-induced cytotoxicity. Moreover, even some hydrophobic bile acids, such as chenodeoxycholic acid also exhibited cytoprotection. It is possible that the cytotoxicity of hydrophobic bile acids is ameliorated by more hydrophilic bile acids under certain conditions. The understanding of the precise mechanism of this phenomenon remains to be determined.

Bile Acids and Salts↗

PubMedDate not supplied

Operative indications for patients with refractory or severe ulcerative colitis.

BACKGROUND/AIMS: The failure of medical treatment for severe ulcerative colitis (UC) can result in an emergency colectomy. Since new treatments using cyclosporin A and leukocytapheresis have been developed, we analyzed historical changes in the operative indications for UC. METHODOLOGY: We retrospectively reviewed the medical record of 40 patients who underwent surgery, and analyzed the medical treatments before surgery using two groups (urgent and elective) and two time periods (1986-1999, 2000-2003). RESULTS: The number of patients who received operations in the severe UC group from 1986 to 1999 was 17 out of 23 patients, but this number decreased from 2000 to 2003. Although 40% of the patients from 2000 to 2003 in the refractory UC group had been treated with steroids only, the mean times of high-dose steroid therapy decreased from 4.3 to 2.5. The total amount of steroids administered in both groups tended to decrease from 2000 onwards. The postoperative questionnaire indicated that about half of them felt that their surgery had been performed too late. CONCLUSIONS: The number of emergency colectomies for severe UC has been decreasing with the introduction of new therapies, but gastroenterologists should carefully monitor the potentially adverse effects of steroids for refractory UC.

Adolescent↗