Fluoxetine for maintenance of remission and to improve quality of life in patients with Crohn's Disease: a pilot randomized placebo-controlled trial

Background and Aims: Previous studies have shown that antidepressants reduce inflammation in animal models of colitis. The present trial aimed to examine whether fluoxetine added to standard therapy for Crohn's disease [CD] maintained remission, improved quality of life [QoL] and/or mental health in people with CD as compared to placebo. Methods: A parallel randomized double-blind placebo controlled trial was conducted. Participants with clinically established CD, with quiescent or only mild disease, were randomly assigned to receive either fluoxetine 20 mg daily or placebo, and followed for 12 months. Participants provided blood and stool samples and completed mental health and QoL questionnaires. Immune functions were assessed by stimulated cytokine secretion [CD3/CD28 stimulation] and flow cytometry for cell type. Linear mixed-effects models were used to compare groups. Results: Of the 26 participants, 14 were randomized to receive fluoxetine and 12 to placebo. Overall, 14 [54%] participants were male. The mean age was 37.4 [SD=13.2] years. Fluoxetine had no effect on inflammatory bowel disease activity measured using either the Crohn's Disease Activity Index [F(3, 27.5)= 0.064, p=0.978] or faecal calprotectin [F(3, 32.5)=1.08, p=0.371], but did have modest effects on immune function. There was no effect of fluoxetine on physical, psychological, social or environmental QoL, anxiety or depressive symptoms as compared to placebo [all p>0.05]. Conclusions: In this small pilot clinical trial, fluoxetine was not superior to placebo in maintaining remission or improving QoL

Microstructure, precipitate and property evolution in cold-rolled Ti-V high strength low alloy steel

A cold-rolled Ti-V high strength low alloy (HSLA) steel was isothermally annealed at 650 °C and 700 °C for different times. A unique combination of techniques including visible light microscopy (VLM), transmission electron microscopy (TEM), matrix dissolution, small angle neutron scattering (SANS) and hardness measurement has been employed to investigate the evolution of microstructure, hardness and precipitate composition, size and volume fraction. Results show that recrystallization is completed after annealing 8 h at 650 °C and 30 min at 700 °C. Three types of precipitates were identified: large Ti(C,N), medium-size (Ti,V)(C,N) and small (Ti,V)C. The Ti/(Ti+V) atomic ratio in the (Ti,V)C precipitates decreases with increasing radius in the 1–15 nm range, which can be explained by the initial nucleation of a TiC-rich core. The average size of the (Ti,V)C precipitates increases, whereas the number density decreases during annealing. The volume fractions of the three types of precipitates were separately determined by the matrix dissolution method. The volume fractions of (Ti,V)C precipitates obtained by matrix dissolution are comparable even slightly more accurate than those obtained by SANS. The hardness first increases and then decreases when annealing at both temperatures, which can be correlated well with the observed microstructural and precipitate evolution.</p

Colonic migrating motor complexes are inhibited in acute tri-nitro benzene sulphonic acid colitis

Published: June 22, 2018Background Inflammatory Bowel Disease (IBD) is characterized by overt inflammation of the intestine and is typically accompanied by symptoms of bloody diarrhea, abdominal pain and cramping. The Colonic Migrating Motor Complex (CMMC) directs the movement of colonic luminal contents over long distances. The tri-nitrobenzene sulphonic acid (TNBS) model of colitis causes inflammatory damage to enteric nerves, however it remains to be determined whether these changes translate to functional outcomes in CMMC activity. We aimed to visualize innate immune cell infiltration into the colon using two-photon laser scanning intra-vital microscopy, and to determine whether CMMC activity is altered in the tri-nitro benzene sulphonic (TNBS) model of colitis. Methods Epithelial barrier permeability was compared between TNBS treated and healthy control mice in-vitro and in-vivo. Innate immune activation was determined by ELISA, flow cytometry and by 2-photon intravital microscopy. The effects of TNBS treatment and IL-1β on CMMC function were determined using a specialized organ bath. Results TNBS colitis increased epithelial barrier permeability in-vitro and in-vivo. Colonic IL-1β concentrations, colonic and systemic CD11b+ cell infiltration, and the number of migrating CD11b+ cells on colonic blood vessels were all increased in TNBS treated mice relative to controls. CMMC frequency and amplitude were inhibited in the distal and mid colon of TNBS treated mice. CMMC activity was not altered by superfusion with IL-1β. Conclusions TNBS colitis damages the epithelial barrier and increases innate immune cell activation in the colon and systemically. Innate cell migration into the colon is readily identifiable by two-photon intra-vital microscopy. CMMC are inhibited by inflammation, but this is not due to direct effects of IL-1β.Ben R. Hofma, Hannah R. Wardill, Chris Mavrangelos, Melissa A. Campaniello, David Dimasi, Joanne M. Bowen, Scott D. Smid, Claudine S. Bonder, Elizabeth A. Beckett, Patrick A. Hughe

Hybrid materials for molecular sieves

Hybrid microporous organosilica membranes for molecular separations made by acid-catalyzed solgel synthesis from bridged silsesquioxane precursors have demonstrated good performance in terms of flux and selectivity and remarkable hydrothermal stability in various pervaporation and gas separation processes. The availability of wide range of α,ω-bis(trialkoxysilyl)alkane and 1,4-bis (triethoxysilyl)benzene precursors allows tuning of membrane properties such as pore size and chemistry. This chapter presents an overview of the synthesis and application of hybrid organosilica microporous membranes in liquid and gas separation processes. After a concise discussion of the history of solgel-derived microporous ceramic membranes for molecular separations, the solgel chemistry of bridged silsesquioxanes and all relevant processing steps needed to obtain a supported microporous films suitable for molecular separations are discussed. The performance of these membranes is correlated with the membrane compositional properties, such as nature, stiffness and length of the bridging group, and details of the solgel process

Longitudinal analysis indicates symptom severity influences immune profile in irritable bowel syndrome

Chris Mavrangelos, Melissa A Campaniello, Jane M Andrews, Peter A Bampton, Patrick A Hughe

Proteolytic activation of IL-1 beta impairs epithelial barrier integrity in the ulcerative colitis lumen

AbstractP A Hughes, H R Wardill, N Dmochowska, C Mavrangelos, M Campaniello, J M Bowen, S Smid, S P Costello, J M Andrew

Fecal supernatants from active ulcerative colitis patients impair colonic epithelial barrier integrity and activate pelvic mucosal extrinsic afferent nerves

Hannah R Wardill, Nicole Dmochowska, Melissa A Campaniello, Chris Mavrangelos, Joanne M Bowen, Jane M Andrews, Sam P Costello, and Patrick A Hughe