Biomedical subjects

T Tsujikawa

Publications and source records attributed to T Tsujikawa.

At least 19 recordsLinked to original sources

PubMed2001

Medium-chain triglyceride-rich enteral nutrition is more effective than low-fat enteral nutrition in rat colitis, but is equal in enteritis.

BACKGROUND: Although enteral nutrition (EN) therapy for Crohn's disease has been confirmed to be as effective as steroid therapy, the precise mechanism responsible for the effects of EN remains unclear, although some of the therapeutic effects of EN are believed to be due to a low dietary fat content. In order to elucidate the influence of fat in EN, it is important to investigate not only the quantity of fat, but also the source of the fat. METHODS: We compared two enteral nutritional formulae: Elental (Ajinomoto) (elemental diet; ED), which contains only 1.5% fat, provided as long-chain triglycerides (LCT), versus Twinline (Snow Brand Milk Products) (TL), which contains a high percentage of fat (20.4%), provided mainly as medium-chain triglycerides (MCT). These formulae were tested on rat enteritis and rat colitis induced by trinitrobenzene sulfonic acid (TNBS). RESULTS: Both ED and TL reduced the manifestations of enteritis. TL had a stronger anti-inflammatory effect than ED for colitis. TL also had nutritional advantages as compared with ED, as shown by the total serum protein in the TL group being significantly higher than that in the ED group. CONCLUSION: The results indicate that intraluminal MCT is suitable as a fat energy source during intestinal inflammation in rats. We suggest that Twinline may be more useful to improve nutritional status and to reduce the mucosal inflammation in rat colitis, but that Twinline is equal in effect to Elental for rat enteritis.

Animals↗

PubMed2001

A case of toxic shock-like syndrome presenting with serious hypoproteinaemia because of a protein-losing gastroenteropathy.

A 37-year-old man was admitted to our hospital because of toxic shock-like syndrome (TSLS) induced by Streptococcus pyogenes. After the pathogenic bacteria had been eradicated, serious diarrhoea appeared and a protein-losing gastroenteropathy developed. An immunohistochemical study of the biopsy specimens of both small and large intestines revealed the infiltration of T-lymphocytes, predominantly CD8+ cells, into the lamina propria of affected mucosa, villus atrophy and crypt hyperplasia. Considering these histological findings, some immunological mechanism which lead the activation of cytotoxic T-lymphocytes may play an important role in the pathogenesis of this rare intestinal manifestation of TSLS.

Adult↗

PubMed2001

Evaluation of intestinal mucosal function by measuring expired (14)CO(2) after oral administration of (14)C-putrescine.

BACKGROUND: Diamine oxidase (DAO) is the enzyme that degrades putrescine, the key main product of polyamine metabolism, and reflects enterocytic maturity of absorption because diamine oxidase activity is highest in the small intestine. We have already shown that expired (14)CO(2) after oral administration of (14)C-putrescine correlated with intestinal DAO activity. However, the influence of food composition and the mucosal adaptation after intestinal resection have not been elucidated. METHODS: Male Wistar rats were fed normal chow or an elemental diet (ED) for 2 weeks. Resected rats underwent 50% jejunectomy or 50% ilectomy. Expired (14)CO(2) levels, following oral administration of (14)C-putrescine were measured in all rats, and compared with the intestinal DAO activity and other mucosal parameters. RESULTS: In the ED group, the (14)CO(2) levels reached a peak earlier, and values were 2.9-fold higher than in the group fed with normal chow. Mucosal alkaline phosphatase (ALP) and DAO activity in the ED group were also higher than in the group fed normal chow, although the mucosal wet weight was significantly lower in the ED group. In the resection groups, all expired (14)CO(2) values increased during measurement. The peak (14)CO(2) values in the jejunectomy group shifted earlier in the postoperative period. The mucosal DAO activity in both the resection groups was higher than it was in the control group at the fifth and 10th postoperative day. However, there were no differences among the three groups at the 15th postoperative day. CONCLUSIONS: Our studies suggested that expired (14)CO(2) after oral administration of (14)C-putrescine correlates with mucosal DAO activity, and that it also reflects intestinal function.

Administration, Oral↗

PubMed2001

Sequential changes in luminal microflora and mucosal cytokine expression during developing of colitis in HLA-B27/beta2-microglobulin transgenic rats.

BACKGROUND: Transgenic rats expressing HLA-B27 and human beta2-microglobulin (HLA-B27 rats) spontaneously develop chronic colitis resembling human inflammatory bowel disease. We investigated the sequential changes in the luminal bacterial flora and mucosal cytokine mRNA expression in this model. METHODS: HLA-B27 rats were maintained in a specific pathogen-free environment, and luminal microflora was evaluated by standard bacterial culture technique. The expression of mucosal cytokine mRNA was analysed by RT-PCR methods. RESULTS: Clinical symptoms of colitis appeared at 8 weeks of age. The total number of obligate anaerobes was higher than those of facultative anaerobes during the experimental period. At 6 weeks of age, the colonization of Bacteroides spp., Bifidobacterium spp. and Lactobacillus spp. was already detectable at high concentrations, whereas Clostridium spp. and Eubacterium spp. were not detected. The expression of proinflammatory cytokines (IL-Ibeta, IL-8 and TNF-alpha) appeared at 8 weeks of age, and these were detectable until 17 weeks. A similar pattern was observed in the expression of Th1 cytokines (IL-2, IL-12 and IFN-gamma). On the other hand, the expression of Th2 cytokines (IL-4, IL-10 and TGF-beta) was weak. IL-4 mRNA expression was weakly detectable only at 6 and 8 weeks of age. The expression of IL-10 and TGF-beta mRNA was scarcely detectable throughout the experimental period. CONCLUSION: The development of colitis may be mediated by both the predominant expression of Th1 cytokines and the weakness of Th2 cytokine expression in the mucosa. The colonization of anaerobic bacteria, especially Bacteroides spp., may be initiating and promoting these cytokine responses.

Animals↗

PubMed2001

Alterations in intestinal microflora, faecal bile acids and short chain fatty acids in dextran sulphate sodium-induced experimental acute colitis in rats.

BACKGROUND: The physiological effects on faecal bile acids and short chain fatty acids (SCFAs) or intestinal microflora in dextran sulphate sodium (DSS)-induced colitis remain unknown and are an area of interest DESIGN ALTERATIONS: of these parameters in DSS-induced colitis in rats were evaluated. METHODS: Male Sprague-Dawley rats (n = 10) were given a 3% DSS aqueous solution orally for 7 days. The concentrations of bile acids and SCFAs in the faeces were measured using gas chromatography and high-performance liquid chromatography. Intestinal microflora, especially anaerobes, were investigated by microbiological methods. RESULTS: On day 7, the concentrations of lithocholic acid and alpha-muricholic acid were significantly decreased and that of cholic acid was significantly increased. There was a strong correlation between the concentration of cholic acid and the macroscopic area of damaged tissue in the colon (R = 0.74, P < 0.05). With respect to SCFAs, DSS administration significantly decreased the concentrations of acetic acid and n-butyric acid. There was also some correlation between the concentration of acetic acid and macroscopic damaged area in the colon (R = -0.60, P = 0.07). Bacteriological studies revealed significantly decreased eubacteria, bifidobacteria and total anaerobes after the administration of DSS. In contrast, lactobacilli were significantly increased. CONCLUSIONS: With the progression of DSS-induced colitis, faecal bile acids, SCFAs and intestinal microflora were altered. It is possible that these alterations contribute in part to the progression of DSS-induced colitis.

Acute Disease↗

PubMed2001

Epithelial expression of caveolin-2, but not caveolin-1, is enhanced in the inflamed mucosa of patients with ulcerative colitis.

Caveolae are vesicular invaginations of the plasma membrane that act as a scaffold of the assembly of many classes of signaling molecules. Caveolins are the principal structural component of caveolae membranes, and three distinct forms of caveolins have been identified: caveolin-1, caveolin-2, and caveolin-3. In this study, we evaluated the changes in the caveolin-1 and caveolin-2 expression in the inflamed mucosa of patients with IBD. Tissue samples were obtained endoscopically from patients with ulcerative colitis (UC) (n = 18), Crohn's disease (n = 10) and ischemic colitis (n = 8). Normal colorectal tissues were also obtained (n = 15). The caveolin expression was evaluated by standard immunohistochemical procedure. In normal colonic mucosa, caveolin-1 expression was detected in the smooth-muscle cells of the muscularis mucosae and the endothelial cells, but caveolin-2 expression was not detected. In the inflamed mucosa of patients with active UC, caveolin-2 expression was clearly detectable as small scattered foci on the luminal surfaces of epithelial cells, but caveolin-1 expression was similar to that in normal mucosa. Caveolin-2 expression increased in accordance with the disease activity of UC. This enhanced caveolin-2 expression was not detected in active Crohn's disease or ischemic colitis. In conclusion, we demonstrated that the epithelial expression of caveolin-2 is markedly enhanced in the inflamed mucosa of patients with UC. It is likely that the enhanced caveolin-2 expression in patients with UC was associated with the altered signal transductions in the intestinal epithelial cells. Furthermore, our results suggest that there are differences in the phenotypic features of epithelial cells between UC and Crohn's disease.

Caveolin 1↗

PubMed2001

Role of complement activation and mast cell degranulation in the pathogenesis of rapid intestinal ischemia/reperfusion injury in rats.

The aim of this study is to define the putative role of complement activation and mucosal mast cell (MMC) degranulation in the pathogenesis of rapid ischemia-reperfusion (I/R) injury. We prepared complement activity-depleted rats by the administration of the anti-complementary agent K-76COONa. To assess the role of MMC degranulation, we used the MMC stabilizer MAR-99 and genetically mast cell-deficient Ws/Ws rats. Autoperfused segments of the jejunum were exposed to 60 min of ischemia, followed by 60 min reperfusion. The epithelial permeability was assessed by (51)Cr-EDTA clearance rate, and the number of MMC was immunohistochemically assessed. I/R treatment induced a marked increase in mucosal permeability and MMC degranulation. The treatment with K-76COONa and MAR-99 significantly attenuated these changes. Furthermore, in Ws/Ws rats the increase in mucosal permeability and MMC degranulation was significantly attenuated. These findings indicate the role of complement activation and MMC activation in the pathogenesis of rapid intestinal I/R injury. A regulation of the complement activation and MMC degranulation may be one of the clinical strategies for prevention of I/R-induced mucosal injury.

Animals↗

PubMed2000

Enhancement of brush border membrane peptidase activity in rat jejunum induced by starvation.

Conflicting results have been obtained in previous studies concerning the adaptation of intestinal blush border membrane enzymes to starvation. This study was designed to clarity the changes in these enzymes under starvation conditions, using a molecular biological approach. Sprague-Dawley rats were starved or given total parenteral nutrition (TPN) for 5 days. Rats allowed free access to food were used as controls. Changes in the activity and expression of jejunal brush border membrane enzymes were compared between three groups. In the starved group, aminopeptidase N and dipeptidyl peptidase IV activity was significantly elevated to 177% and 166%, respectively, of control values. In contrast, sucrase and maltase activity was significantly decreased. The activity of these peptidases also tended to be increased at the renal brush border membrane. Up-regulation of peptidase activity was not evident in the TPN group. Western and Northern blot analysis revealed that the changes in aminopeptidase N activity were attributable to increases in the protein and mRNA level. The activity and expression of brush border membrane peptidases in rat jejunum is up-regulated during starvation, and these changes are considered to be an effect of whole-body malnourishment, rather than an absence of luminal nutrition.

Aminopeptidases↗

PubMed2000

Clinical importance of n-3 fatty acid-rich diet and nutritional education for the maintenance of remission in Crohn's disease.

Elemental diet (ED) therapy has been established as primary therapy for Crohn's disease, and home enteral nutrition (HEN) has been reported to control relapse at a dose of more than 30kcal/kg of ideal body weight. However, a decrease in ED compliance with long-term use is becoming problem. We developed an n-3 fatty acid-rich diet and carried out nutritional education specifically for Crohn's disease patients using HEN to facilitate compliance and to improve their nutritional status. After the introduction of this n-3 rich diet, disease activity was not altered, and nutritional status, especially serum n-3 fatty acid levels, improved. The remission periods in patients with poor compliance seemed to be prolonged by the nutritional education. Thus, a n-3 rich diet in combination with nutritional education specific for Crohn's disease patients is very important for the in maintenance of high compliance and for maintaining nutritional balance.

Adolescent↗

PubMed2000

Efficacy of oral adsorbent for treatment of peristomal fistula associated with Crohn's disease.

Perianal fistulae are frequently seen complications in Crohn's disease. Although surgical procedures such as Seton's method have been devised, many patients still suffer from fistulae that are resistant to conventional therapy. We administered oral adsorbent to a patient with disease Crohn's who had a complicated peristomal fistula that did not improve with conventional therapy. Six grams of oral adsorbent (AST-120) were added daily to a regimen of elemental diet therapy and prednisolone. The fistula gradually decreased in size after the administration of the oral adsorbent, and had healed completely after 40 days' treatment. There were no side effects from the oral adsorbent. This case report suggests that oral adsorbent is an effective treatment for peristomal fistula associated with Crohn's disease.

Administration, Oral↗

PubMed2000

Preventive efficacy of butyrate enemas and oral administration of Clostridium butyricum M588 in dextran sodium sulfate-induced colitis in rats.

Butyrate enemas have been reported to be effective in ulcerative colitis. However, long-term use is difficult because of the troublesome procedure and the unpleasant smell. We therefore investigated the effects of the oral administration of Clostridium butyricum M588 (CBM588), an enterobacterium producing butyrate, in dextran sodium sulfate (DSS)-induced colitis in rats. First, we confirmed the effects of pre-treatment with a butyrate enema on DSS colitis. We then studied the efficacy of oral administration of CBM588 which was started 1 week prior to the induction of DSS colitis. In the CBM588 group, the ulcer index and myeloperoxidase (MPO) activity in the distal colon were significantly lower than in the control group. Proliferating cell nuclear antigen (PCNA) immuno-positive cells were increased around the ulcer in the CBM588 group. In regard to the contents of the cecum and colon, the proportions of Lactobacillus and Eubacterium were increased in the cecum in the CBM588 group. Further, there were significant increases of n-butyrate, propionate, and acetate concentrations in the cecum in the CBM588 group. These results indicated that the oral administration of CBM588 alleviated DSS-induced colitis, and may be useful instead of butyrate enema.

Acetates↗

PubMed2000

Therapeutic effects of an oral adsorbent on acute dextran sulphate sodium-induced colitis and its recovery phase in rats, especially effects of elimination of bile acids in gut lumen.

BACKGROUND: The pathogenesis of inflammatory bowel disease is still unknown. However, it is possible that faecal bile acids influence the clinical course. AIMS: To evaluate the eliminating effects of faecal bile acids by the oral adsorbent on dextran sulphate sodium-induced rat colitis. METHODS: Rats were given 3% dextran sulphate sodium aqueous solution for 7 days, with or without concomitant administration of oral adsorbent, or the rats were given dextran sulphate sodium for 7 days, followed with or without oral adsorbent for 5 days. Macroscopic and microscopic examinations of the colons and measurement of faecal bile acids were performed. The cytotoxicity of bile salts on Caco-2 cells was also evaluated. RESULTS: Oral adsorbent tended to attenuate the dextran sulphate sodium-induced colitis. Oral adsorbent was fairly effective in reducing faecal hyodeoxycholic acid concentration. A positive correlation was found between the size of the ulcer area and the faecal hyodeoxycholic acid concentration. In a cell culture study, cytotoxicity of bile acid was parallel with increasing hydrophobicity of the bile acid. However, hyodeoxycholate exhibited severe cytotoxicity, despite its hydrophilic properties. CONCLUSIONS: Oral adsorbent tended to attenuate the dextran sulphate sodium-induced colitis and tended to promote the recovery process. It is possible that bile acids in the gut lumen influence the progression of dextran sulphate sodium-induced colitis and its repair process.

Acute Disease↗

PubMed2000

Haemorrhagic cerebral sinus thrombosis associated with ulcerative colitis: a case report of successful treatment by anticoagulant therapy.

A 29-year-old man with ulcerative colitis was admitted to our hospital because of convulsions and a headache. Before admission, oral prednisolone had been administered due to his ulcerative colitis relapse. Computed tomography revealed a low-density area in the right frontal pole suggestive of a venous infarction. Once his headache and convulsions improved after the administration of an antiepileptic drug, he began to complain of right arm numbness and right hemianopsia again. An urgent magnetic resonance imaging angiograph showed extensive thrombosis in the superior sagittal sinus. We finally used the anticoagulant agents, heparin and urokinase, which eased his complaints and prevented the development of bloody stools. He was discharged with no neurological symptoms 25 days after admission. This is a rare case of sinus thrombosis complicated by ulcerative colitis, in which anticoagulant therapy was successful. Magnetic resonance imaging angiography was useful for the diagnosis and for evaluating the therapeutic effect.

Adult↗

PubMed2000

Medium- and long-chain fatty acids differentially modulate interleukin-8 secretion in human fetal intestinal epithelial cells.

The primary therapeutic effects of enteral nutrition in patients with Crohn's disease have been reported previously. Although the quantity and type of fat in enteral nutrition are considered to be important, it is unclear how fat modulates mucosal inflammatory responses in the intestine. In the present study, we evaluated the effects of medium-chain and long-chain fatty acids (MCFA and LCFA) on interleukin (IL)-8 secretion in a fetal intestinal epithelial cell line, intestine-407 cells. IL-8 expression was evaluated at the protein and mRNA levels. The activation of nuclear factor-kappaB was assessed with an electrophoretic gel mobility shift assay. The addition of oleic acid (LCFA) micelles, but not octanoic acid (MCFA) micelles, weakly but significantly enhanced basal IL-8 secretion in the intestine-407 cells. The addition of MCFA (5 mmol/L) induced a 40% increase in IL-1beta-induced IL-8 secretion and a 35% increase in tumor necrosis factor (TNF)-alpha-induced IL-8 secretion, respectively. The addition of LCFA (5 mmol/L) induced a 140% increase in IL-1beta-induced IL-8 secretion and a 110% increase in TNF-alpha-induced IL-8 secretion, respectively. These responses were also observed at the mRNA levels. The electrophoretic gel mobility shift assay indicated that both MCFA and LCFA enhanced IL-1beta- and TNF-alpha-induced nuclear factor-kappaB activation. We demonstrated the proinflammatory activities of MCFA and especially LCFA. It is likely that medium-chain triglycerides may be more suitable than long-chain triglycerides as an energy source in enteral diets in the treatment of patients with Crohn's disease.

Cells, Cultured↗

PubMed2000

Regulation of PepT1 peptide transporter expression in the rat small intestine under malnourished conditions.

BACKGROUND AND AIMS: Many investigations suggested that peptide nutrition had a clinical advantage for nitrogen absorption. Recently, the cDNA encoding the H(+)/peptide cotransporter PepT1 was cloned. However, the regulatory mechanism of PepT1 expression under malnourished conditions has not been elucidated. The aim of this study was to clarify regulatory mechanisms of PepT1 expression. METHODS: Sprague-Dawley rats were starved for 4 days, semistarved (50% amount of control) for 10 days, or given total parenteral nutrition (TPN) for 10 days. Rats with free feeding were used as control. Among those groups, the changes of PepT1 mRNA level in the jejunal mucosa and PepT1 protein density at the brush-border membranes were examined by Northern blot and by Western blot analysis, respectively. RESULTS: Both starvation and TPN treatment caused a significant decrease in mucosal weight by 41 and 50% respectively. PepT1 mRNA level increased to 179% in the starved group and also to 161 and 164% in the TPN and semistarved groups, respectively. In contrast, sodium-dependent glucose transporter 1 mRNA expression showed no significant change. PepT1 protein density showed similar changes with the mRNA. CONCLUSIONS: PepT1 gene expression was significantly enhanced under the malnourished conditions in spite of atrophic changes of intestinal mucosa.

Animals↗

PubMed2000

Meningitis carcinomatosa originating from an alpha fetoprotein-producing gastric cancer.

Alpha fetoprotein (AFP)-producing gastric cancer is relatively rare and meningitis carcinomatosa is similarly a rare manifestation among the neoplastic diseases. There have been no previous reports of meningitis carcinomatosa originating from AFP-producing gastric cancer. A 68-year-old man with AFP-producing gastric cancer was treated with cisplatin and doxifluridine because of multiple liver metastases. Although the liver lesion was reduced to 30% of pretreatment size after 6 courses of chemotherapy, meningitis carcinomatosa subsequently occurred. Immunostaining of AFP and magnetic resonance imaging (MRI) were useful in the diagnosis of meningitis caused by AFP producing cancer cells.

Adenocarcinoma↗

PubMed1999

Changes in serum diamine oxidase activity during chemotherapy in patients with hematological malignancies.

Serum diamine oxidase (DAO) activity is very low, but is considered to reflect quantitative changes in small intestinal mass. Therefore, we measured DAO activity during chemotherapy in patients with hematological malignancies in order to evaluate mucosal injury. DAO activity decreased from 1-3 weeks after chemotherapy but returned to initial levels after 4 weeks. As the dosage of anti-cancer drugs increased, DAO activity decreased more, but its activity was not related to other parameters. These findings suggest that serum DAO could be used as an indicator of mucosal injury during chemotherapy.

Adult↗

PubMed1999

Medium-chain triglycerides modulate ileitis induced by trinitrobenzene sulfonic acid.

BACKGROUND: It is important to develop an appropriate animal model for further investigation into inflammatory bowel disease (IBD). We therefore investigated a trinitrobenzene sulfonic acid (TNBS) ileitis model. Dietary fat in Crohn's disease is still a controversial risk factor for IBD. We therefore also studied the effects of medium-chain triglycerides (MCT) and long-chain triglycerides (LCT) on TNBS ileitis. METHODS AND RESULTS: An intraileal injection of TNBS induced ulceration and inflammation with thickening of the intestinal wall, which were characterized histologically by infiltration of polymorphic nuclear leucocytes and by granuloma formation. The mucosal damage score and serum sialic acid levels reached their highest 7 days after the TNBS injection and then gradually decreased. The mucosal damage series in the MCT group was significantly lower than in the LCT group, and levels of tumour necrosis factor-alpha (TNF-alpha) and leukotriene B4 (LTB4) tended to be lower in the MCT group. CONCLUSIONS: These results suggested that TNBS enteritis might be useful as an IBD animal model and that MCT modulates intestinal inflammation and is less damaging than LCT.

Analysis of Variance↗