Yong-Ho Nah

Expression of protease-activated receptor 2 in ulcerative colitis

Although tryptase released from mast cells might play a key role in the pathogenesis of ulcerative colitis (UC), the role of protease-activated receptor 2 (PAR2), tryptase receptor, remains unclear in the pathogenesis of this disease. The expressions of PAR2 and tumor necrosis factor (TNF) &agr; in nine UC tissues and nine normal tissues were examined by immunohistochemistry. TNF-&agr; levels secreted from human leukemic mast cell line (HMC-1) after the treatment of PAR2 agonists were also measured by enzyme-linked immunosorbent assay. The PAR2 and TNF-&agr; proteins were more significantly detectable in UC tissues than in normal tissues. Furthermore, 65.2% of PAR2+ cells and 66.4% of TNF-&agr;+ cells in UC tissues were tryptase-positive cells. In other words, 60.6% and 46.3% of tryptase-positive cells in UC tissues were PAR2+ cells and TNF-&agr;+ cells, respectively. A &khgr;2 analysis showed correlation (p < 0.007) between PAR2 and TNF-&agr; in tryptase-positive mast cells. Moreover, PAR2 agonists significantly induced the TNF-&agr; secretion from HMC-1. These results indicate that the activation of the mast cells through PAR2 may be involved in the pathogenesis of UC.

The role of gastrointestinal endoscopy in long-distance runners with gastrointestinal symptoms.

Background Exercise-related gastrointestinal symptoms are not uncommon among athletes. The occurrence of gastrointestinal bleeding has been reported, especially in long-distance runners. We studied gastrointestinal mucosal damage, using gastrointestinal endoscopy, in competitive long-distance runners. Gastrointestinal blood loss and anaemia before and after running were also assessed. Methods Sixteen competitive long-distance runners (all men; age range 16–19 years) participated in the study. All runners completed a symptom questionnaire prior to a 20 km race. Stool occult blood and haematological studies (haemoglobin, haematocrit, serum iron, total iron-binding capacity [TIBC] and ferritin) were performed before and immediately after the race. Gastrointestinal endoscopy was performed to assess macroscopic changes. Colonoscopy was also performed on the patients who had positive stool occult blood before or after the race. Results Gastrointestinal symptoms were frequently experienced by the runners. Gastritis (n = 16), oesophagitis (n = 6) and gastric ulcer (n = 1) were found at gastroscopy. Colonoscopy was performed on four patients who had positive stool occult blood. One had multiple erosions at the splenic flexure and one had a rectal polyp. Five runners had anaemia, and all of these had at least one endoscopic lesion (three gastritis, two oesophagitis and one multiple erosion at the splenic flexure). There were significant changes in the following haematological parameters after the race: iron (decreased, P = 0.02), ferritin (decreased, P = 0.001) and TIBC (increased, P = 0.00005). Conclusions Gastrointestinal symptoms and gastrointestinal mucosal damage are prevalent among long-distance runners. Prior to treatment, gastrointestinal endoscopy should be considered in long-distance runners with gastrointestinal symptoms and/or anaemia.

Stress, coping, and depression in non-ulcer dyspepsia patients.

Thirty adults with upper gastrointestinal symptoms in the absence of structural organic disease diagnosed with non-ulcer dyspepsia (NUD) were compared to 30 healthy adults who had visited the hepatobiliary clinic for medical evaluation of non-organic complaints without NUD. Medical investigation in both groups were negative. Before independent gastrointestinal physicians conducted diagnostic evaluations, all subjects were evaluated for anxiety and depressive symptoms, stressful life events, coping style, and social support. The measures included Symptom Checklist 90-Revised (SCL-90-R), Beck Depression Inventory (BDI), Spielberger State-Trait Anxiety Inventory (STAI), Ways of Coping Checklist, and Interpersonal Support Evaluation List, and a self-report questionnaire, which measured the quantity of perceived stressful life events. The NUD patients reported significantly more symptoms of depression, more perceived stressful life events, less problem-focused coping, and less social support than the control subjects. Depressive symptoms were negatively correlated with interpersonal support, whereas, problem-focused coping was positively correlated with interpersonal support in the NUD patients. The two groups did not differ significantly in terms of anxiety and emotion-focused coping. The implications of these findings for the diagnosis and treatment of NUD are discussed.

Involvement of p38 MAP kinase during iron chelator-mediated apoptotic cell death.

Iron is an essential element for the neoplastic cell growth, and iron chelators have been tested for their potential anti-proliferative and cytotoxic effects. To determine the mechanism of cell death induced by iron chelators, we explored the pathways of the three structurally related mitogen-activated protein (MAP) kinase subfamilies during apoptosis induced by iron chelators. We report that the chelator deferoxamine (DFO) strongly activates both p38 MAP kinase and extracellular signal-regulated kinase (ERK) at an early stage of incubation, but slightly activates c-Jun N-terminal kinase/stress-activated protein kinase (JNK/SAPK) at a late stage of incubation. Among three MAP kinase blockers used, however, the selective p38 MAP kinase inhibitor SB203580 could only protect HL-60 cells from chelator-induced cell death, indicating that p38 MAP kinase serves as a major mediator of apoptosis induced by iron chelator. DFO also caused release of cytochrome c from mitochondria and induced activation of caspase 3 and caspase 8. Interestingly, treatment of HL-60 cells with SB203580 greatly abolished cytochrome c release, and activation of caspase 3 and caspase 8. Collectively, the current study reveals that p38 MAP kinase plays an important role in iron chelator-mediated cell death of HL-60 cells by activating downstream apoptotic cascade that executes cell death pathway.

The aqueous extract of Solanum melongena inhibits PAR2 agonist-induced inflammation.

BACKGROUND Solanum melongena L. (Solanaceae) has antioxidant, analgesic, hypolipidemic and antiallergic activity. METHODS The anti-inflammatory effects of the water extract of the S. melongena (SMWE) were investigated in PAR2-mediated mouse paw edema. Paw edema was induced by injection of trypsin or trans-cinnamoyl-LIGRLO-NH(2) (tc-NH(2)) into the hindpaw of mice. The SMWE (1, 5, 10, and 100 mg/kg) was orally administered 1 h before induction of inflammation. RESULTS At doses of 5, 10, and 100 mg/kg, the SMWE showed significant inhibition of both paw edema and vascular permeability. The SMWE (10 mg/kg) significantly also inhibited PAR2 agonist-induced myeloperoxidase (MPO) activity and tumor necrosis factor (TNF)-alpha expression in paw tissue. CONCLUSION These results demonstrate that the SMWE inhibits PAR2 agonist-induced mouse paw edema.

Inhibition of trypsin-induced mast cell activation by water fraction of Lonicera japonica.

Lonicera japonica Thunb.(Caprifoliaceae) has long been known as an anti-inflammatory. In the present study, the effect of water fraction ofLonicera japonica (LJ) on trypsin-induced mast cell activation was examined. HMC-1 cells were stimulated with trypsin (100 nM) in the presence or absence of LJ (10, 100, and 1000 μg/mL). TNF-α and tryptase production were measured by enzyme-linked immunosorbent assay (ELISA) and reverse transcription-PCR. Extracellular signal-regulated kinase (ERK) phosphorylation was assessed by Western blot. Trypsin activity was measured by using Bz-DL-Arg-p-nitroanilide (BAPNA) as substrate. LJ (10, 100, and 1000 μg/mL) inhibited TNF-α secretion in a dose-dependent manner. LJ (10, 100, and 1000 μg/mL) also inhibited TNF-α and tryptase mRNA expression in trypsin-stimulated HMC-1. Furthermore, LJ inhibited trypsin-induced ERK phosphorylation. However, LJ did not affect the trypsin activity even 1000 μg/mL. These results indicate that LJ may inhibit trypsin-induced mast cell activation through the inhibition of ERK phosphorylation than the inhibition of trypsin activity.

The effect of chronic variable stress on bowel habit and adrenal function in rats

Background and Aim:  Increased colonic motility is a well‐known stress response and corticotropin releasing hormone plays an important role in this response, but sequential change of bowel habit and adrenal function during chronic stress has not been reported. The objective of this study was to evaluate the effect of chronic stress on bowel habit and adrenal function.

Pyopneumopericardium Due to an Esophagopericardial Fistula With a Fish Bone

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Catalposide, A compound isolated from Catalpa ovata, attenuates induction of intestinal epithelial proinflammatory gene expression and reduces the severity of trinitrobenzene sulfonic acid-induced colitis in mice

Certain irinoid-producing plants have been used as herbal anti-inflammatory remedies. Here we evaluated whether catalposide (CATP), a single compound isolated from irinoid-producing plant Catalpa ovata, has a potential for preventing or ameliorating diseases characterized by mucosal inflammation. Preliminary microarray-based gene expression test revealed that CATP, which alone did not significantly affect expression of any of the >8,000 genes analyzed, attenuated the expression of tumor necrosis factor-&agr; (TNF-&agr;)-induced proinflammatory genes including interleukin-8 (IL-8) in human intestinal epithelial HT-29 cells. Down-regulation of IL-8 mRNA accumulation was also reflected by the decreased IL-8 secretion in CATP-treated HT-29 cells. The signal transduction study revealed that CATP significantly attenuates TNF-&agr;-mediated p38 and extracellular signal-regulated kinase (ERK) phosphorylation. Further, CATP reduced NF-κB-mediated transcriptional activation as well as Iκ-B&agr; degradation. To establish the in vivo relevance of these findings, we examined whether CATP could affect intestinal inflammation in vivo using the mouse model of trinitrobenzene sulfonic acid (TNBS)-induced inflammatory colitis. Intrarectal administration of CATP dramatically reduced the weight loss, colonic damage, and mucosal ulceration that characterize TNBS colitis. Moreover, CATP suppressed the expression of TNF-&agr;, interleukin-1β, and intercellular adhesion molecule-1 along with the inhibition of NF-κ B p65 translocation into nucleus in TNBS colitis. Collectively, current results demonstrate that CATP may be an effective agent for the treatment of diseases characterized by mucosal inflammation.