Kazuhiro Katada

Whole-Brain Perfusion CT Performed with a Prototype 256–Detector Row CT System: Initial Experience

PURPOSE To preliminarily evaluate the feasibility and potential diagnostic utility of whole-brain perfusion computed tomography (CT) performed with a prototype 256-detector row CT system over an extended range covering the entire brain to assess ischemic cerebrovascular disease. MATERIALS AND METHODS Institutional review board approval and informed consent were obtained. Eleven cases in 10 subjects (six men, four women; mean age, 64.3 years) with intra- or extracranial stenosis were retrospectively evaluated with whole-brain perfusion CT. Three readers independently evaluated perfusion CT data. The diagnostic performance of perfusion CT was visually evaluated with a three-point scale used to assess three factors. Differences between four axial perfusion CT images obtained at the basal ganglia level (hereafter, four-section images) and whole-brain perfusion CT images were assessed with the paired t test. In four subjects, the interval between perfusion CT and single photon emission computed tomography (SPECT) was 1-17 days (mean, 10.3 days). Correlation between perfusion CT findings and SPECT findings was assessed with the Spearman correlation coefficient. RESULTS Three-dimensional perfusion CT images and axial, coronal, and sagittal whole-brain perfusion CT images were displayed, and the extent of ischemia was assessed. Mean visual evaluation scores were significantly higher for whole-brain images than for four-section images (4.27 +/- 0.76 [standard deviation] vs 2.55 +/- 0.87). The cerebral blood flow ratios of the ischemic lesions relative to normal regions scanned with perfusion CT (x) and SPECT (y) showed a significant positive correlation (R(2) = 0.76, y = 0.44 x + 0.37, P < .001). CONCLUSION Perfusion CT performed with a 256-detector row CT system can be used to assess the entire brain with administration of one contrast medium bolus. Thus, ischemic regions can be identified with one examination, which has the potential to improve diagnostic utility.

Noninvasive Coronary Angiography With a Prototype 256-Row Area Detector Computed Tomography System Comparison With Conventional Invasive Coronary Angiography

To the Editor: Since the initial reports describing the usefulness of computed tomography angiography (CTA) with 4-row multislice compute tomography (MSCT) for the examination of the coronary arteries, the number of detector rows has been further increased. Now, 256-row area detector CT (256-row CT

Ability of a novel blue laser imaging system for the diagnosis of colorectal polyps.

A new endoscope system with a laser light source, blue laser imaging (BLI), has been developed by Fujifilm that allows for narrow‐band light observation. The aim of the present study was to evaluate the utility of BLI for the diagnosis of colorectal polyps.

BTB and CNC homolog 1 (Bach1) deficiency ameliorates TNBS colitis in mice: role of M2 macrophages and heme oxygenase-1.

Background:BTB and CNC homolog 1 (Bach1) is a transcriptional repressor of heme oxygenase-1 (HO-1), which plays an important role in the protection of cells and tissues against acute and chronic inflammation. However, the role of Bach1 in the gastrointestinal mucosal defense system remains little understood. HO-1 supports the suppression of experimental colitis and localizes mainly in macrophages in colonic mucosa. This study was undertaken to elucidate the Bach1/HO-1 systems effects on the pathogenesis of experimental colitis. Methods:This study used C57BL/6 (wild-type) and homozygous Bach1-deficient C57BL/6 mice in which colonic damage was induced by the administration of an enema of 2,4,6-trinitrobenzene sulfonic acid (TNBS). Subsequently, they were evaluated macroscopically, histologically, and biochemically. Peritoneal macrophages from the respective mice were isolated and analyzed. Then, wild-type mice were injected with peritoneal macrophages from the respective mice. Acute colitis was induced similarly. Results:TNBS-induced colitis was inhibited in Bach1-deficient mice. TNBS administration increased the expression of HO-1 messenger RNA and protein in colonic mucosa in Bach1-deficient mice. The expression of HO-1 mainly localized in F4/80-immunopositive and CD11b-immunopositive macrophages. Isolated peritoneal macrophages from Bach1-deficient mice highly expressed HO-1 and also manifested M2 macrophage markers, such as Arginase-1, Fizz-1, Ym1, and MRC1. Furthermore, TNBS-induced colitis was inhibited by the transfer of Bach1-deficient macrophages into wild-type mice. Conclusions:Deficiency of Bach1 ameliorated TNBS-induced colitis. Bach1-deficient macrophages played a key role in protection against colitis. Targeting of this mechanism is applicable to cell therapy for human inflammatory bowel disease.

Heme oxygenase-1 (Hsp32) is involved in the protection of small intestine by whole body mild hyperthermia from ischemia/reperfusion injury in rat.

Aim: The aim of the present study was to explore whether heme oxygenase-1 (HO-1) is involved in the hyperthermia-provided protection of the small intestine from ischemia/reperfusion injury in rats. Methods: Intestinal damage was induced in male Sprague-Dawley rats by clamping both the superior mesenteric artery and the celiac trunk for 30 min, followed by reperfusion. Whole-body hyperthermia was induced in anesthetized rats by placement in a temperature-controlled water bath. Whole-body hyperthermia to a core temperature of 42–43°C for 15 min was followed by passive cooling. We started the hyperthermic treatment 6 h before the vascular clamping. The severity of the mucosal injury was evaluated by several biochemical markers and histological findings. Hyperthermia-induced heat-shock proteins were detected by Western blotting. We also investigated the effect of zinc protoporphyrin IX (an HO-1 inhibitor) on the protective effect of hyperthermia. Results: The rats, which were killed after ischemia/reperfusion, had severe intestinal inflammation. Hyperthermia significantly induced the production of Hsp70 and HO-1 in intestinal mucosa and significantly reduced ischemia/reperfusion-induced mucosal injury. The combination of zinc protoporphyrin IX with hyperthermia extinguished the protective effects of hyperthermia on ischemia/reperfusion injury. Conclusion: Hyperthermia protects against ischemia/reperfusion injury in rat small intestine through the expression of heat-shock proteins, especially HO-1.

Helicobacter pylori Activates Gastric Epithelial Cells to Produce Interleukin-8 via Protease-Activated Receptor 2

Background/Aim: Recently, it has been shown that serine proteases derived from microorganisms stimulate epithelial cells to produce inflammatory mediators through protease-activated receptor (PAR). We investigated the involvement of PAR2 in the interleukin (IL)-8 production by Helicobacter pylori-infected gastric epithelial cells. Methods and Results: Human gastric epithelial cells, MKN45 cells, were used. The expression of PAR2 was assessed by real-time PCR and immunocytochemistry, and IL-8 protein was measured by an enzyme-linked immunosorbent assay. PAR2 mRNA and protein were constitutively expressed on unstimulated MKN45 cells. The treatment of cells with H. pylori resulted in a significant increase in PAR2 expression. In addition, trypsin (a natural PAR2 agonist), SLIGKV amide (a synthetic PAR2 agonist), H. pylori live bacteria or H. pylori culture supernatant significantly induced IL-8 production from MKN45 cells. H. pylori-induced IL-8 production was inhibited by nafamostat mesilate (a serine protease inhibitor), neutralizing antibody to PAR2 and in PAR2-deficient cells treated with siRNA. Conclusions: These results reveal that H. pylori-derived protease activates gastric epithelial cells to produce inflammatory cytokines through PAR2, suggesting an important role for PAR2 in the modulation of gastric inflammation associated with H. pylori.

Endoscopic mucosal resection with 0.13% hyaluronic acid solution for colorectal polyps less than 20 mm: a randomized controlled trial.

Background and Aim:  Adequate mucosal elevation by submucosal injection is important for definitive en bloc resection and prevention of perforation during endoscopic mucosal resection (EMR). The objective of this study is to determine the efficacy of 0.13% hyaluronic acid (HA) solution for high and sustained mucosal elevation during colorectal EMR.

Acetyl salicylic acid induces damage to intestinal epithelial cells by oxidation-related modifications of ZO-1

Acetyl salicylic acid (ASA) is one of the most frequently prescribed medications for the secondary prevention of cardiovascular and cerebrovascular events. It has recently been reported to cause small intestinal mucosal injury at a considerably higher rate than previously believed. The aim of this study is to investigate the mechanism by which this occurs using an in vitro small intestine model focusing on the role of oxidative stress and cell permeability. Differentiated Caco-2 exhibits a phenotype similar to human small intestinal epithelium. We measured whether ASA induced the increase of differentiated Caco-2 permeability, the decrease of tight junction protein expression, the production of reactive oxygen species (ROS), and the expression of ROS-modified zonula occludens-1 (ZO-1) protein. In some experiments, Mn(III) tetrakis(1-methyl-4-pyridyl)porphyrin (MnTMPyP, a superoxide dismutase mimetic) was used. The nontoxic concentration of ASA decreased transepithelial electrical resistance and increased the flux of fluorescein isothiocyanate-conjugated dextran across Caco-2 in a time-dependent manner. The same concentration of ASA significantly decreased ZO-1 expression among TJ proteins as assessed by Western blot and immunocytochemistry and increased ROS production and the expression of oxidative stress-modified ZO-1 protein. However, MnTMPyP suppressed the ASA-induced increased intercellular permeability and the ASA-induced ROS-modified ZO-1 expression. Our findings indicate that ASA-induced ROS production can specifically modify the expression of ZO-1 protein and induce increased cell permeability, which may ultimately cause small intestinal mucosal injury.

Hyperthermia attenuates TNF-alpha-induced up regulation of endothelial cell adhesion molecules in human arterial endothelial cells

Background and aim: The activation of NF-κB induces production of inflammatory cytokines and up regulation of endothelial cell adhesion molecules (ECAM). ECAM (e.g., E-selectin, VCAM-1 and ICAM-1) associates to the recruitment of leukocytes into tissue exposed to inflammatory situation. In this study, we investigated the effects of hyperthermia on the activation of NF-κB and the up regulation of E-selectin and VCAM-1 in human endothelial cells stimulated by TNF-α. Methods: Human arterial endothelial cells (HAEC) were pretreated with hyperthermia for 60 min at 42°C, followed by incubation at 37°C in a passively cooled incubator, before TNF-α stimulation. To assess the effects of hyperthermia on TNF-α-induced up regulation of ECAM and TNF-α-induced activation of NF-κB, we measured ECAM by ELISA, and evaluated the activation of NF-κB by Western blotting after TNF-α stimulation. The accumulation of HO-1, Hsp70 and IκBα in hyperthermia-treated HAEC was also assessed by Western blotting. To investigate the role of Hsp70, we treated HAEC with geranylgeranylacetone (GGA, Hsp70 inducer) 2 h before hyperthermia, and then measured ECAM in TNF-α-stimulated HAEC by ELISA. Results: Pretreatment of hyperthermia reduced TNF-α-induced up regulation of E-selectin and VCAM-1. In addition, accumulation of Hsp70, HO-1 and IκBα protein were up-regulated after hyperthermia. Furthermore, Western blotting analysis revealed that pretreatment of hyperthermia attenuated TNF-α-induced translocation of p65 into the nuclei of HAEC. Moreover, GGA enhanced Hsp70 accumulation induced by hyperthermia. Hyperthermia pretreatment combined with GGA induced further inhibition of TNF-α-induced up regulation of ECAM when compared with hyperthermia alone. Conclusion: Pretreatment of hyperthermia blocks TNF-α-induced NF-κB activation, resulting in the inhibition of ECAM up regulation in HAEC.

Dextran sulfate sodium-induced acute colonic inflammation in angiotensin II type 1a receptor deficient mice

Abstract.Objective:Angiotensin II (Ang II) receptor blockers have been reported to contribute to cytoprotective effects in various organs. However, the role of renin-angiotensin system (RAS) in modulation of the inflammatory bowel disease (IBD) remains unclear. In this study we assessed the role of angiotensin II type 1a (AT1a) receptor on the outcome of dextran sulfate sodium (DSS)-induced acute colitis by employing AT1a receptor deficient mice.Materials and methods:The acute colitis was induced in wild type (WT) and AT1a receptor deficient mice by giving orally 3% DSS in drinking water for 7 days.Results:Induction of DSS colitis resulted in up-regulation of Ang II and AT1a receptor in the colonic mucosa of WT mice. In parallel, loss of body weight, an increase in disease activity index (DAI), and the shortening of colon were found in DSS-challenged WT mice. In addition, an increase in thiobarbituric acid (TBA)-reactive substances and myeloperoxidase (MPO) activity, along with the up-regulation of tumor necrosis factor (TNF)-α were detected in the colonic mucosa of DSS-challenged WT mice. The endpoints mentioned above were significantly ameliorated in DSS-challenged AT1a receptor deficient mice.Conclusions:RAS is involved in the pathophysiology of DSS-induced colitis and AT1a receptor may be a novel therapeutic target for the treatment of IBD.