Supplementary Material for: Effects of Perfluorocarbon Use during Rhegmatogenous Retinal Detachment Surgery on Postoperative Outcomes

Introduction: The aim of this study was to determine whether the use of perfluorocarbon liquid (PFCL) affects the rate of retinal re-attachments after an initial attachment by vitrectomy in eyes with rhegmatogenous retinal detachment (RRD). Methods: This was a retrospective, observational, multicenter study of 3,446 eyes registered in the Japanese vitreoretinal surgery treatment information database. Of these, 2,648 eyes had undergone vitrectomy as the first surgery for RRD. The re-attachment rates after the primary vitrectomy with or without PFCL were evaluated. In addition, the significance of factors affecting the re-detachments was determined by univariate and multivariate analyses. The measured outcomes were the rates of re-attachments after the primary vitrectomy with or without the use of PFCL. Results: A total of 2,362 eyes in the database were analyzed: 325 had and 2,037 did not have PFCL injected into the vitreous cavity during the vitrectomy. The rate of re-attachments was 91.5% in the PFCL group and 93.2% in the non-PFCL group (p = 0.46, χ2 test). Although there were several risk factors associated with the re-detachments in eyes without PFCL (p t tests, and Fisher’s exact tests), they were not associated in eyes with PFCL use. However, multivariate analyses showed that there was no significant association between the use and the non-use of PFCL in the rate of re-detachments (β = −0.08, p = 0.46). Conclusions: The use of PFCL during the initial vitrectomy for RRD does not affect the rate of re-attachments

Supplementary Material for: Guggulsterone, a Plant-Derived Inhibitor of NF-TB, Suppresses CDX2 and COX-2 Expression and Reduces the Viability of Esophageal Adenocarcinoma Cells

<b><i>Background/Aims:</i></b> Induction by bile acid of caudal type homeobox 2 (CDX2) and cyclooxygenase-2 (COX-2) expression via nuclear factor-TB (NF-TB) activation is a critical event in the development of Barrett's esophagus (BE) and esophageal adenocarcinoma (EAC). Guggulsterone (GS) is a plant sterol that inhibits NF-TB activity. Here, we evaluated whether GS has either or both chemopreventive or therapeutic effects against EAC. <b><i>Methods:</i></b> Two EAC cells lines were treated with deoxycholic acid (DCA) in the presence of GS or vehicle. The levels of transcription and translation of <i>ITBE</i>, <i>CDX2</i>, and <i>COX-2</i> were determined. Prostaglandin E₂ (PGE₂) levels, cell viability, and cell cycle distribution were assessed as well. <b><i>Results:</i></b> GS inhibited DCA-induced ITBE phosphorylation. GS and the NF-TB inhibitor BAY11-7085 suppressed DCA-induced <i>CDX2</i> and <i>COX-2</i> expression in EAC cells. GS also suppressed basal transcription levels of <i>CDX2</i> and <i>COX-2</i> and reduced constitutive synthesis of COX-2 and PGE₂. Further, GS reduced the viability of EAC cells, increased their numbers in the apoptotic sub-G1 fraction. <b><i>Conclusion:</i></b> GS suppressed DCA-induced and NF-TB-dependent activation of <i>CDX2</i> and <i>COX-2</i> expression. Further, GS also reduced the viability of EAC cells. GS may serve as candidate for preventing and treating EAC and BE. i 2014 S. Karger AG, Base

Erratum: 1,25-Dihydroxyvitamin D₃ Upregulates Functional C-X-C Chemokine Receptor Type 4 Expression in Human Eosinophils

<b><i>Background:</i></b> Epidemiological studies suggest that vitamin D may be protective against the inception and exacerbation of allergic diseases. However, the direct effect of vitamin D on eosinophils, the major effector cells in allergic inflammation, is not known. It has been reported that C-X-C chemokine receptor type 4 (CXCR4) in eosinophils is induced in non-Th2 cytokine milieu or in response to glucocorticoids, recruiting the cell to noninflammatory sites. <b><i>Objectives:</i></b> To test whether 1,25-dihydroxyvitamin D₃ [1,25-(OH)₂D₃ or calcitriol], the active metabolite of vitamin D, acts directly on eosinophils to induce upregulation of CXCR4. <b><i>Methods:</i></b> Peripheral blood eosinophils from normal volunteers were isolated by CD16 immunomagnetic beads. Vitamin D receptor (VDR) expression was detected by RT-PCR. Eosinophils were cultured with 1,25-(OH)₂D₃ and the survival and expression of CXCR4 on eosinophils were measured by flowcytometry. Eosinophil migration by CXCL-12/SDF-1 in the presence of 1,25-(OH)₂D₃ was also analyzed. <b><i>Results:</i></b> Eosinophils expressed VDR. 1,25-(OH)₂D₃ prolonged eosinophil survival and upregulated eosinophil surface expression of CXCR4 in a concentration-dependent manner. Interleukin (IL)-5 significantly reduced CXCR4 expression and migration induced by the ligand CXCL-12/SDF-1. 1,25-(OH)₂D₃ reversed the negative effects of IL-5 on the CXCR4-CXCL12 pathway. <b><i>Conclusion:</i></b> 1,25-(OH)₂D₃ regulates CXCR4 expression in eosinophils. The mechanism may be involved in eosinophil recruitment to noninflammatory sites where the ligand of CXCR4 is constitutively expressed

PowerPoint Slides for: Severity of Gastric Mucosal Atrophy Is the Major Determinant of Plasma Ghrelin Level in Hemodialysis Patients

<i>Background:</i> Ghrelin, an orexigenic hormone, has multiple favorable functions including protein anabolism enhancement, anti-inflammatory actions, and cardiovascular protection. A low plasma ghrelin level is associated with increased mortality in patients treated with hemodialysis (HD). However, it is unclear whether the plasma ghrelin level in HD patients correlates with the severity of gastric mucosal atrophy and <i>Helicobacter pylori</i> status. <i>Methods:</i> Seventy-eight maintenance HD patients and 51 non-dialysis patients with chronic kidney disease were evaluated for severity of gastric mucosal atrophy by gastroduodenoscopy and for <i>H. pylori</i> status using an anti-<i>H. pylori</i>-antibody and rapid urease test. Plasma acyl and des-acyl ghrelin levels were measured and their associations with relevant clinical parameters were investigated. <i>Results:</i> Des-acyl ghrelin level in HD patients was significantly higher than that in patients with kidney function preserved. Although acyl and des-acyl ghrelin levels were similar between current <i>H. pylori </i>positive and negative HD patients, both levels decreased significantly with the progress of endoscopic gastric mucosal atrophy in HD patients. Serum pepsinogen (PG) I level and PG I/II ratio decreased significantly according to the severity of atrophy in HD patients and positively significantly correlated with both ghrelin levels. Multiple regression analysis showed significant positive correlations between acyl ghrelin and PG I levels (β = 0.738, p < 0.001) and significant negative correlations between ghrelin and age, albumin, and creatinine levels. <i>Conclusions:</i> Gastric atrophy is the major determinant of ghrelin level in HD patients. Management practices, such as <i>H. pylori</i> eradication, before advanced atrophy may be required to prevent the decrease of ghrelin levels and improve the prognosis of HD patients

Erratum: Reduced Abundance of Butyrate-Producing Bacteria Species in the Fecal Microbial Community in Crohn's Disease

<b><i>Background:</i></b> The global alteration of the gut microbial community (dysbiosis) plays an important role in the pathogenesis of inflammatory bowel diseases (IBDs). However, bacterial species that characterize dysbiosis in IBD remain unclear. In this study, we assessed the alteration of the fecal microbiota profile in patients with Crohn's disease (CD) using 16S rRNA sequencing. <b><i>Summary:</i></b> Fecal samples from 10 inactive CD patients and 10 healthy individuals were subjected to 16S rRNA sequencing. The V3-V4 hypervariable regions of 16S rRNA were sequenced by the Illumina MiSeq™II system. The average of 62,201 reads per CD sample was significantly lower than the average of 73,716 reads per control sample. The genera <i>Bacteroides</i>, <i>Eubacterium</i>, <i>Faecalibacterium</i> and <i>Ruminococcus</i> significantly decreased in CD patients as compared to healthy controls. In contrast, the genera <i>Actinomyces</i> and <i>Bifidobacterium</i> significantly increased in CD patients. At the species level, butyrate-producing bacterial species, such as <i>Blautia faecis</i>, <i>Roseburia inulinivorans</i>, <i>Ruminococcus torques</i>, <i>Clostridium lavalense</i>, <i>Bacteroides uniformis</i> and <i>Faecalibacterium prausnitzii</i> were significantly reduced in CD patients as compared to healthy individuals (p < 0.05). These results of 16S rRNA sequencing were confirmed in additional CD patients (n = 68) and in healthy controls (n = 46) using quantitative PCR. The abundance of <i>Roseburia inulinivorans</i> and <i>Ruminococcus torques</i> was significantly lower in C-reactive protein (CRP)-positive CD patients as compared to CRP-negative CD patients (p < 0.05). <b><i>Key Message:</i></b> The dysbiosis of CD patients is characterized by reduced abundance of multiple butyrate-producing bacteria species

Supplementary Material for: Histological Properties of Main and Accessory Olfactory Bulbs in the Common Hippopotamus

The olfactory system of mammals comprises a main olfactory system that detects hundreds of odorants and a vomeronasal system that detects specific chemicals such as pheromones. The main (MOB) and accessory (AOB) olfactory bulbs are the respective primary centers of the main olfactory and vomeronasal systems. Most mammals including artiodactyls possess a large MOB and a comparatively small AOB, whereas most cetaceans lack olfactory bulbs. The common hippopotamus (<i>Hippopotamus amphibius</i>) is semiaquatic and belongs to the order Cetartiodactyla, family Hippopotamidae, which seems to be the closest extant family to cetaceans. The present study evaluates the significance of the olfactory system in the hippopotamus by histologically analyzing the MOB and AOB of a male common hippopotamus. The MOB comprised six layers (olfactory nerve, glomerular, external plexiform, mitral cell, internal plexiform, and granule cell), and the AOB comprised vomeronasal nerve, glomerular, plexiform, and granule cell layers. The MOB contained mitral cells and tufted cells, and the AOB possessed mitral/tufted cells. These histological features of the MOB and the AOB were similar to those in most artiodactyls. All glomeruli in the AOB were positive for anti-Gαi2, but weakly positive for anti-Gαo, suggesting that the hippopotamus vomeronasal system expresses vomeronasal type 1 receptors with a high affinity for volatile compounds. These findings suggest that the olfactory system of the hippopotamus is as well developed as that of other artiodactyl species and that the hippopotamus might depend on its olfactory system for terrestrial social communication