Gastrointestinal diseases

Abstract

BACKGROUND: Previous studies have revealed the activation of neutral sphingomyelinase (N-SMase)/ceramide pathway in hepatic tissue following warm liver ischemia reperfusion (IR) injury. Excessive ceramide accumulation is known to potentiate apoptotic stimuli and a link between apoptosis and endoplasmic reticulum (ER) stress has been established in hepatic IR injury. Thus, this study determined the role of selective N-SMase inhibition on ER stress and apoptotic markers in a rat model of liver IR injury. METHODS: Selective N-SMase inhibitor was administered via intraperitoneal injections. Liver IR injury was created by clamping blood vessels supplying the median and left lateral hepatic lobes for 60 min, followed by 60 min reperfusion. Levels of sphingmyelin and ceramide in liver tissue were determined by an optimized multiple reaction monitoring (MRM) method using ultra fast-liquid chromatography (UFLC) coupled with tandem mass spectrometry (MS/MS). Electron microscopic immunohistochemistry and quantitative PCR analysis was performed to evaluate ER stress markers while TUNEL analysis and immunoassay was used to examine apoptosis. RESULTS: Spingomyelin levels were significantly increased in all IR groups compared to controls. Treatment with a specific N-SMase inhibitor significantly decreased all measured ceramides in IR injury. A significant increase was observed in ER stress markers C/EBP-homologous protein (CHOP) and 78 kDa glucose-regulated protein (GRP78) in IR injury, which was not significantly altered by N-SMase inhibition. Inhibition of N-SMase caused a significant reduction in phospho-NFkB levels, hepatic TUNEL staining, cytosolic cytochrome c and caspase-3, -8 and -9 activities which were significantly increased in IR injury. CONCLUSIONS: Data herein confirm the role of ceramide in increased apoptotic cell death and highlight the protective effect of N-SMase inhibition in down-regulation of apoptotic stimuli responses occurring in hepatic IR injury.Poster Abstracts -EuroMedLab Athens 2017 -Athens, 11-15 June 2017 • DOI 10.1515/cclm-2017-5018 Clin Chem Lab Med 2017 55, Special Suppl, pp S1 -S1121, June 2017 BACKGROUNDThe Faecal Immunochemical Test (FIT) for haemoglobin is widely used in screening of colorectal cancer (CRC) but presently there are just few studies regarding its usefulness in symptomatic patients and in surveillance. The different characteristics of populations: screening, surveillance and symptomatic, recommends evaluate the performance of FIT in this different groups of patients. This study evaluates FIT performance in two group of patients. A cohort of patients in surveillance for familiar history of CRC or history of adenomas or CRC with regular colonoscopies and a cohort of symptomatic patients with an indication of diagnostic or therapeutic colonoscopy. METHODSWe have evaluated 967 faecal samples from 484 patients. 433 samples corresponding to patients in surveillance, mean age was 61 years (32-88 years) and the 58.2% of samples corresponding to women and 534 samples corresponding...