Comparison of short-term outcomes of robotic and laparoscopic transabdominal peritoneal repair for unilateral inguinal hernia: a propensity-score matched analysis.

PURPOSE: This study aimed to compare perioperative outcomes of robotic and laparoscopic transabdominal peritoneal repair (TAPP) for unilateral inguinal hernia. METHODS: This single institutional retrospective cohort study used de-identified data of patients who underwent robotic TAPP (R-TAPP) or laparoscopic TAPP (L-TAPP) for unilateral inguinal hernia between January 1, 2016 and October 31, 2021. Two cohorts were propensity matched, and data were analyzed. The learning curve was evaluated in the R-TAPP group. RESULTS: Among 938 patients analyzed, 704 were included. After propensity-score matching, 80 patients were included in each group. The difference in operative time between R-TAPP and L-TAPP groups was 10 min (99.5 and 89.5 min, p = 0.087); however, console/laparoscopic time was similar (67 and 66 min, p = 0.71). The dissection time for medial-type hernia in the R-TAPP group was marginally shorter than that in the L-TAPP group (17 and 27 min, p = 0.056); however, there was no difference for lateral-type hernia (38.5 and 40 min p = 0.37). Perioperative variables, including estimated blood loss, postoperative hospital stay, and postoperative pain, had no significant difference, and chronic pain, which needed medication or intervention, was not observed in each group. The number of cases needed to achieve plateau performance was 7-10 in the R-TAPP group. CONCLUSION: This study suggests that R-TAPP was safely introduced, and its perioperative outcomes were not inferior to those of L-TAPP. A shorter dissection time for medial-type hernia might be due to the robot's advantages, and a fast-learning curve could help with the early standardization of the procedure.

Determining an optimal dose of linaclotide for use in Japanese patients with irritable bowel syndrome with constipation: A phase II randomized, double-blind, placebo-controlled study.

BACKGROUND: Clinical testing to determine a suitable dose of linaclotide for Japanese patients with irritable bowel syndrome with constipation (IBS-C) was needed. METHODS: This was a randomized, double-blind, placebo-controlled, dose-finding trial. Japanese patients with IBS-C diagnosed using Rome III criteria (n = 559, men/women: 49/510) were randomly assigned to 1 of 4 linaclotide doses (0.0625, 0.125, 0.25, or 0.5 mg) or placebo for the 12-week treatment period. The primary endpoint was responder rate of global assessment of relief of IBS symptoms during 12 weeks. The secondary endpoints included responder rates of complete spontaneous bowel movement (CSBM), SBM and abdominal pain/discomfort relief and others. KEY RESULTS: The primary endpoint was 23.2%, 36.2%, 38.7%, 34.8%, and 38.3% in placebo (n = 112), 0.0625 (n = 116), 0.125 (n = 111), 0.25 (n = 112), and 0.5 (n = 107) mg of linaclotide groups with the difference from the placebo group in each linaclotide group (13.0%, 15.5%, 11.6%, 15.1%, P > .05). Monthly responder rate of global assessment of relief of IBS symptoms at month 3 (48.6%), responder rate of CSBM during 12 weeks (45.8%), and responder rate of abdominal pain/discomfort relief during 12 weeks (32.7%) in the 0.5 mg were significantly higher than those in placebo group (29.5%, P < .01; 25.9%, P < .01; and 18.8%, P < .05 respectively). The most frequent adverse event in the linaclotide groups was diarrhea. CONCLUSIONS & INFERENCES: This study suggests that a linaclotide dose of 0.5 mg may be appropriate in Japanese patients with IBS-C.

Regulation of eotaxin-3/CC chemokine ligand 26 expression by T helper type 2 cytokines in human colonic myofibroblasts.

Eotaxins induce the trafficking of eosinophils to the sites of inflammation via CC chemokine receptor 3 (CCR3). In this study, we investigated eotaxin-3/CC chemokine ligand 26 (CCL26) expression in the inflamed mucosa of patients with inflammatory bowel disease (IBD), and characterized the molecular mechanisms responsible for eotaxin-3 expression in human colonic myofibroblasts. Eotaxin-3 mRNA and protein expression was evaluated by real time-polymerase chain reaction (PCR) and enzyme-linked immunosorbent assay (ELISA), respectively. Eotaxin-3 mRNA expression was elevated significantly in the active lesions of ulcerative colitis (UC) patients. Significant elevations were also observed in the active lesions of Crohn's disease (CD) patients, but this was significantly lower than that detected in the active UC lesions. There were no significant increases in the inactive lesions of UC or CD patients. Colonic myofibroblasts were identified as a major source of eotaxin-3 in the colonic mucosa, and interleukin (IL)-4 and IL-13 enhanced eotaxin-3 mRNA and protein expression significantly in these cells. There was a significant positive correlation between mucosal eotaxin-3 and IL-4 mRNA expression in the active lesions of IBD patients. The IL-4- and IL-13-induced eotaxin-3 mRNA expression was regulated by the signal transducer and activator of transcription-6 (STAT-6) and suppressor of cytokine signalling (SOCS)1-mediated pathways. Interferon (IFN)-γ acts as a negative regulator on the IL-4- and IL-13-induced eotaxin-3 expression via STAT-1 activation. Eotaxin-3 expression was elevated specifically in the active lesions of IBD, in particular UC. Eotaxin-3 derived from colonic myofibroblasts may play an important role in the pathophysiology of UC.

Epithelial expression of interleukin-37b in inflammatory bowel disease.

Interleukin (IL)-37 is a member of the IL-1 cytokine family. We investigated IL-37b expression in the inflamed mucosa of inflammatory bowel disease (IBD) patients. Furthermore, we analysed IL-37b expression in human colonic epithelial cells. The human colonic epithelial cell line T84 and human colonic subepithelial myofibroblasts (SEMFs) were used. IL-37b expression in the IBD mucosa was evaluated by immunohistochemistry. IL-37b mRNA and protein expression were determined by real time-polymerase chain reaction (PCR) and Western blotting, respectively. IL-37b was not detected in the normal colonic mucosa. In the inflamed mucosa of IBD patients, epithelial IL-37b expression was increased markedly. In ulcerative colitis (UC) and Crohn's disease (CD) patients, IL-37b expression was enhanced in the affected mucosa. In the intestinal epithelial cell line T84, the expression of IL-37b mRNA and protein was enhanced by tumour necrosis factor (TNF)-α. This IL-37b induction by TNF-α was mediated by nuclear factor (NF)-κB and activator protein (AP)-1 activation. Furthermore, IL-37b inhibited TNF-α-induced interferon-γ-inducible protein (IP)-10 expression significantly in human colonic SEMFs. Epithelial IL-37b expression was increased in IBD patients, especially UC patients. IL-37b may be involved in the pathophysiology of IBD as an anti-inflammatory cytokine and an inhibitor of both innate and acquired immune responses.

C/EBPß promotes BCR-ABL-mediated myeloid expansion and leukemic stem cell exhaustion.

The BCR-ABL fusion oncoprotein accelerates differentiation and proliferation of myeloid cells during the chronic phase of chronic myeloid leukemia (CP-CML). Here, the role of CCAAT/enhancer binding protein ß (C/EBPß), a regulator for 'emergency granulopoiesis,' in the pathogenesis of CP-CML was examined. C/EBPß expression was upregulated in Lineage(-) CD34(+) CD38(-) hematopoietic stem cells (HSCs) and myeloid progenitors isolated from bone marrow of patients with CP-CML. In EML cells, a mouse HSC line, BCR-ABL upregulated C/EBPß, at least in part, through the activation of STAT5. Myeloid differentiation and proliferation induced by BCR-ABL was significantly impaired in C/EBPß-deficient bone marrow cells in vitro. Mice that were transplanted with BCR-ABL-transduced C/EBPß knockout bone marrow cells survived longer than mice that received BCR-ABL-transduced wild-type (WT) bone marrow cells. Significantly higher levels of leukemic stem cells were maintained in BCR-ABL-transduced C/EBPß-deficient cells than in BCR-ABL-transduced WT cells. These results suggest that C/EBPß is involved in BCR-ABL-mediated myeloid expansion. Further elucidation of the molecular mechanisms underlying the C/EBPß-mediated stem cell loss might reveal a novel therapeutic strategy for eradication of CML stem cells.

Faecal chitinase 3-like-1: a novel biomarker of disease activity in paediatric inflammatory bowel disease.

BACKGROUND: Chitinase 3-like-1 (CHI3L1) is up-regulated in the inflamed mucosa of inflammatory bowel disease (IBD). AIM: To evaluate the usefulness of a faecal CHI3L1 assay, as a reliable marker for predicting the severity of paediatric IBD. METHODS: Faecal samples were obtained from ulcerative colitis (UC, n = 94), Crohn's disease (CD, n = 87), and healthy individuals (n = 56). The faecal CHI3L1 and calprotectin levels were determined by ELISA. For endoscopic evaluation, the sum of the Matts' score for UC and the simple endoscopic score for CD (SES-CD) were used. Ileal lesions were evaluated by ultrasonography. RESULTS: Faecal CHI3L1 levels were significantly elevated in active UC (median 366.6 ng/g, n = 44) and active CD (median 632.7 ng/g, n = 48) patients, as compared with healthy individuals (median 2.2 ng/g, n = 56). In UC patients, the faecal CHI3L1 levels were positively correlated with the sum of the Matts' score (r = 0.73, P < 0.01, n = 42). In CD patients, there was a significant correlation between faecal CHI3L1 levels and endoscopic activity as determined by the SES-CD scoring system (r = 0.61, P < 0.01, n = 25). The faecal CHI3L1 levels of patients with wall thickening of their small intestine were significantly higher than those of healthy controls or patients without wall thickening. The cutoff value of 13.7 ng/g for fecal CHI3L1(the 95th percentile of the control value) predicted active lesions in IBD patients with a sensitivity of 84.7% and a specificity of 88.9%. CONCLUSION: Faecal CHI3L1 assays may be useful for predicting the severity and activity of mucosal inflammation in IBD.

Glyoxalase-I is a novel target against Bcr-Abl+ leukemic cells acquiring stem-like characteristics in a hypoxic environment.

Abl tyrosine kinase inhibitors (TKIs) such as imatinib and dasatinib are ineffective against Bcr-Abl(+) leukemic stem cells. Thus, the identification of novel agents that are effective in eradicating quiescent Bcr-Abl(+) stem cells is needed to cure leukemias caused by Bcr-Abl(+) cells. Human Bcr-Abl(+) cells engrafted in the bone marrow of immunodeficient mice survive under severe hypoxia. We generated two hypoxia-adapted (HA)-Bcr-Abl(+) sublines by selection in long-term hypoxic cultures (1.0% O(2)). Interestingly, HA-Bcr-Abl(+) cells exhibited stem cell-like characteristics, including more cells in a dormant, increase of side population fraction, higher beta-catenin expression, resistance to Abl TKIs, and a higher transplantation efficiency. Compared with the respective parental cells, HA-Bcr-Abl(+) cells had higher levels of protein and higher enzyme activity of glyoxalase-I (Glo-I), an enzyme that detoxifies methylglyoxal, a cytotoxic by-product of glycolysis. In contrast to Abl TKIs, Glo-I inhibitors were much more effective in killing HA-Bcr-Abl(+) cells both in vitro and in vivo. These findings indicate that Glo-I is a novel molecular target for treatment of Bcr-Abl(+) leukemias, and, in particular, Abl TKI-resistant quiescent Bcr-Abl(+) leukemic cells that have acquired stem-like characteristics in the process of adapting to a hypoxic environment.

The increased mucosal mRNA expressions of complement C3 and interleukin-17 in inflammatory bowel disease.

Recent studies have demonstrated that the complement system participates in the regulation of T cell functions. To address the local biosynthesis of complement components in inflammatory bowel disease (IBD) mucosa, we investigated C3 and interleukin (IL)-17 mRNA expression in mucosal samples obtained from patients with IBD. The molecular mechanisms underlying C3 induction were investigated in human colonic subepithelial myofibroblasts (SEMFs). IL-17 and C3 mRNA expressions in the IBD mucosa were evaluated by real-time polymerase chain reaction. The C3 levels in the supernatant were determined by enzyme-linked immunosorbent assay. IL-17 and C3 mRNA expressions were elevated significantly in the active lesions from ulcerative colitis (UC) and Crohn's disease (CD) patients. There was a significant positive correlation between IL-17 and C3 mRNA expression in the IBD mucosa. IL-17 stimulated a dose- and time-dependent increase in C3 mRNA expression and C3 secretion in colonic SEMFs. The C3 molecules secreted by colonic SEMFs were a 115-kDa alpha-chain linked to a 70-kDa beta-chain by disulphide bonds, which was identical to serum C3. The IL-17-induced C3 mRNA expression was blocked by p42/44 mitogen-activated protein kinase (MAPK) inhibitors (PD98059 and U0216) and a p38 MAPK inhibitor (SB203580). Furthermore, IL-17-induced C3 mRNA expression was inhibited by an adenovirus containing a stable mutant form of I kappaB alpha. C3 and IL-17 mRNA expressions are enhanced, with a strong correlation, in the inflamed mucosa of IBD patients. Part of these clinical findings was considered to be mediated by the colonic SEMF response to IL-17.

Faecal microbiota profile of Crohn's disease determined by terminal restriction fragment length polymorphism analysis.

BACKGROUND: Terminal restriction fragment length polymorphism (T-RFLP) analyses are powerful tools to assess the diversity of complex microbiota. T-RFLPs permit rapid comparisons of microbiota from many samples. AIM: To perform T-RFLP analyses of faecal microbiota in Crohn's disease (CD) patients to investigate potential alterations in faecal microbial communities and furthermore to analyse the effects of elemental diet on faecal microbiota profiles. METHODS: Thirty-four patients with CD and 30 healthy individuals were enrolled in the study. DNA was extracted from stool samples and 16S rRNA genes were amplified by PCR. PCR products were digested with BslI restriction enzymes and T-RF lengths were determined. RESULTS: Faecal microbial communities were classified into seven clusters. Almost all healthy individuals (28/30) were included in cluster I, II and III, but the majority of CD patients (25/34) could be divided into another four clusters (cluster IV-VII). Prediction of bacteria based on the BslI-digested T-RFLP database showed a significant decrease in Clostridium cluster IV, Clostridium cluster XI and subcluster XIVa in CD patients. In contrast, Bacteroides significantly increased in CD patients. Significant increases in Enterobacteriales were also observed in CD patients. Furthermore, elemental diets modulated faecal bacterial communities in CD patients. CONCLUSIONS: Terminal restriction fragment length polymorphism analyses showed that the diversity of faecal microbiota in patients with CD differed from that of healthy individuals. Furthermore, elemental diets modulated faecal microbiota composition, and this effect may be involved in mechanisms of clinical effects of elemental diet.

Novel single-balloon enteroscopy for diagnosis and treatment of the small intestine: preliminary experiences.

BACKGROUND AND AIM: As a tool for examining the small intestine, double-balloon enteroscopy (DBE) has been used routinely. However, there remain a few issues relating to the handling of DBE, such as attaching a balloon to the tip of the scope, and inflating/deflating the two balloon systems. Recently, we developed a novel single-balloon enteroscopy (SBE) system for the examination of the small intestine. The aim of the present study was to evaluate the insertion technique, the safety, and the clinical impact of the SBE system. PATIENTS AND METHODS: Between January 2006 and June 2007, all patients undergoing enteroscopy with the Olympus SBE system (length 200 cm, outer diameter 9.2 mm) were studied. Instead of a balloon attached to the distal scope end, the distal scope end was hook-shaped, and manipulating the up-angle or down-angle of the scope end enabled exploration of the small intestine. RESULTS: A total of 78 procedures were performed in 41 patients (24 men, 17 women; mean age 48.9 years, range 23 - 85 years). The indications for the examination were suspected mid-gastrointestinal bleeding (n = 12), Crohn's disease (n = 17), abdominal pain (n = 8), and abdominal tumor (n = 4). The mean procedure time was 62.8 +/- 20.2 minutes and 70.4 +/- 19.3 minutes for the oral and anal routes, respectively. Among 24 patients in whom total enteroscopy was attempted, the entire small intestine was explored in 6. CONCLUSION: SBE is not only easy to perform, due to the single balloon, but it can also safely examine the deep small intestine. Therefore, SBE may be a useful diagnostic and therapeutic tool in addition to DBE for investigating suspected small bowel disease.

Epithelial overexpression of interleukin-32alpha in inflammatory bowel disease.

Interleukin (IL)-32 is a recently described proinflammatory cytokine, characterized by induction of nuclear factor (NF)-kappaB activation. We studied IL-32alpha expression in the inflamed mucosa of inflammatory bowel disease (IBD). We also investigated mechanisms regulating IL-32alpha expression. Tissue samples were obtained endoscopically or surgically from patients with ulcerative colitis (UC) (n = 10), Crohn's disease (CD) (n = 10), ischaemic colitis (n = 4) and normal colorectal tissues (n = 10). IL-32alpha expression was evaluated by standard immunohistochemical procedure. IL-32 mRNA expression was analysed by Northern blot. IL-32alpha was expressed weakly by colonic epithelial cells from normal individuals and subjects with ischaemic colitis. In the inflamed mucosa of IBD patients, epithelial IL-32alpha expression was increased markedly. In UC and CD patients, IL-32alpha expression was enhanced in affected mucosa compared to non-affected mucosa. In intestinal epithelial cell lines, expression of IL-32alpha mRNA and protein was enhanced by IL-1beta, interferon (IFN)-gamma and tumour necrosis factor (TNF)-alpha. A combination of TNF-alpha plus IFN-gamma exerted synergistic effects. IL-32alpha induction by IL-1beta and/or TNF-alpha was mediated by NF-kappaB activation. Epithelial IL-32alpha expression was increased in IBD patients, and in CD patients in particular. IL-32alpha might be involved in the pathophysiology of IBD as a proinflammatory cytokine and a mediator of innate immune response.

Breath malodor in an asthmatic patient caused by side-effects of medication: a case report and review of the literature.

OBJECTIVE: The purpose of this report is to document the presence of dimethyl sulfide in mouth air as the predominant volatile sulfur compound (VSC) in an asthmatic patient who was regularly taking suplatast tosilate. STUDY DESIGN: The patient was a 33-year-old woman who complained of bad breath. She had been diagnosed as having asthma and was receiving periodical medical examinations once a month. VSC in her mouth air were measured with a gas chromatograph. Oral physiotherapy was also carried out to remove any oral malodor of which the source was intraoral. RESULTS: With the improvement in oral hygiene and periodontal conditions, the level of VSC was reduced but dimethyl sulfide still remained as the predominant VSC. CONCLUSIONS: Dimethyl sulfide metabolized from suplatast tosilate may be a potential cause of halitosis.

Increased expression of interleukin 17 in inflammatory bowel disease.

BACKGROUND AND AIM: Interleukin (IL) 17 is a cytokine which exerts strong proinflammatory activities. In this study we evaluated changes in IL-17 expression in the inflamed mucosa and in the serum of patients with inflammatory bowel disease (IBD). METHODS: Tissue samples were obtained endoscopically or surgically from patients with ulcerative colitis (UC) (n=20), Crohn's disease (CD) (n=20), infectious colitis (n=5), ischaemic colitis (n=8), and normal colorectal tissues (n=15). IL-17 expression was evaluated by a standard immunohistochemical procedure. Serum IL-17 levels were determined by ELISA. IL-17 mRNA expression was analysed by reverse transcriptase-polymerase chain reaction. RESULTS: IL-17 expression was not detected in samples from normal colonic mucosa, infectious colitis, or ischaemic colitis. In the inflamed mucosa of active UC and CD patients, IL-17 expression was clearly detectable in CD3(+) T cells or CD68(+) monocytes/macrophages. The average number of IL-17(+) cells was significantly increased in active UC and CD patients compared with inactive patients. IL-17 mRNA expression was not detected in normal mucosa but was detectable in the mucosa from active UC and CD patients. IL-17 was not detected in the sera from normal individuals, infectious colitis, or ischaemic colitis patients but IL-17 levels were significantly elevated in IBD patients. CONCLUSIONS: IL-17 expression in the mucosa and serum was increased in IBD patients. It is likely that IL-17 expression in IBD may be associated with altered immune and inflammatory responses in the intestinal mucosa.

Combination chemotherapy using carboplatin (JM-8) and etoposide (JET therapy) for recurrent malignant gliomas: a phase II study.

BACKGROUND: To study efficacy and safety of chemotherapy using carboplatin (JM-8) and etoposide ("JET" therapy) for the treatment of recurrent malignant glioma, a phase II study was conducted. Tumour control, survival time, and toxicity/side effects were assessed in patients with recurrent malignant glioma which failed to respond to a postoperative combined auxiliary therapy comprising of IFN-beta, ACNU and radiation. METHODS: Twenty-eight patients, fourteen with anaplastic astrocytoma (AA) and fourteen with glioblastoma (GB) were included in this study. The JET regimen consists of the intravenous administration of carboplatin (300 mg/m(2)) on day 1 and etoposide (60 mg/m(2)) on day 1 to 5, repeated every 6 weeks. FINDINGS: Following the therapy, we observed partial response (PR) in five (36%) of 14 patients with AA and two (14%) of 14 with GB, and stabilization of the disease (SD) in six (43%) in each group. The mean survival/survival after recurrence was 51 months/25 months in the AA group, and 17/9 in the GB group. INTERPRETATIONS: These results compare favorably with the natural course of recurrent malignant glioma. JET shows signs of efficacy in patients with recurrent malignant glioma, and a randomized trial comparing it to standard therapy is warranted.

Interleukin-1beta and tumor necrosis factor-alpha induce chemokine and matrix metalloproteinase gene expression in human colonic subepithelial myofibroblasts.

BACKGROUND: Colonic subepithelial myofibroblasts may play a role in the inflammatory responses and in extracellular matrix (ECM) metabolism. In this study, we investigated the effects of interleukin (IL)-1beta and tumor necrosis factor (TNF)-alpha on chemokine (IL-8 and monocyte chemoattractant protein (MCP)-1) and ECM turnover (proliferation of subepithelial myofibroblasts, and secretion of ECM and matrix metalloproteinases (MMPs)) in colonic subepithelial myofibroblasts. METHODS: Human colonic subepithelial myofibroblasts were isolated using the method described by Mahida et al. Chemokine and MMP expressions were determined by ELISA and Northern blotting. Nuclear factor (NF)-kappaB and NF-IL6 DNA binding activities were evaluated by electrophoretic gel mobility shift assays (EMSA). RESULTS: IL-1beta and TNF-alpha did not affect the proliferation of subepithelial myofibroblasts, but stimulated the secretion of types I and IV collagens weakly. Unstimulated subepithelial myofibroblasts secreted a large amount of MMP-2, but a small amount of IL-8, MCP-1 and MMP-1. IL-1beta and TNF-alpha both induced a dose- and time-dependent increase in IL-8, MCP-1 and MMP-1 secretion, and weakly stimulated MMP-2 secretion. IL-1beta and TNF-alpha both rapidly evoked NF-kappaB DNA-binding activity. The inhibition of NF-kappaB activation markedly blocked both IL-1beta- and TNF-alpha-induced IL-8 and MCP-1 mRNA expression, but did not affect MMP-1 mRNA expression. CONCLUSIONS: These observations indicate that chemokine secretion and ECM metabolism are collectively regulated by the proinflammatory cytokines, IL-1beta and TNF-alpha, in colonic subepithelial myofibroblasts. Thus, colonic subepithelial myofibroblasts may play an important role in the pathophysiology of inflammation in the colon.

Interleukin-17 stimulates chemokine (interleukin-8 and monocyte chemoattractant protein-1) secretion in human pancreatic periacinar myofibroblasts.

BACKGROUND: Interleukin (IL)-17 is a newly identified T-cell-derived cytokine that can regulate the functions of a variety of cell types. In this study, we investigated the effects of CD4+ T-cell-derived cytokines on chemokine secretion in human pancreatic periacinar myofibroblasts. METHODS: The secretion of IL-8 and monocyte chemoattractant protein (MCP)-1 was evaluated by ELISA and Northern blot. The expression of IL-17 receptor (R) was analyzed by Northern blot and a binding assay using 125I-labeled IL-17. The activation of nuclear factor-kappaB (NF-kappaB) was assessed by an electrophoretic gel mobility shift assay (EMSA). RESULTS: IL-17 induced a dose-dependent increase in IL-8 and MCP-1 secretion. The effects of IL-17 on IL-8 and MCP-1 mRNA abundance reached a maximum as early as 3 h. and then gradually decreased. IL-17 and IFN-gamma synergistically increased IL-8 secretion and additively enhanced MCP-1 secretion. IFN-gamma induced a weak increase in IL-17R mRNA abundance, but incubation with IFN-gamma for 24 h had no effects on 125I-labeled IL-17-binding, indicating that the co-stimulatory effects of IL-17 and IFN-gamma were not regulated by the modulation of IL-17R expression. Furthermore, IL-17 induced a rapid increase in NF-kappaB DNA-binding activity, and the combination of IL-17 and IFN-gamma further enhanced NF-kappaB DNA-binding activity. CONCLUSIONS: In conclusion, it becomes clear that IL-17 is an inducer of IL-8 and MCP-1 secretion in human pancreatic periacinar myofibroblasts. The combination of IL-17 with IFN-gamma further enhances chemokine secretion. These findings indicate a linkage between T-cell-mediated immunity and inflammatory responses in the pancreas.

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.

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.

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.