AB0073 INTESTINAL PERMEABILITY IN SPONDYLOARTHRITIS: A SYSTEMATIC REVIEW OF THE LITERATURE

Background:Growing evidence argue for a role of the gut in the pathophysiology of various chronic rheumatic diseases such as spondyloarthritis (SpA). This so-called “gut-joint axis” involves dysbiosis, bacterial translocation, intestinal inflammation and increase in intestinal permeability. Recent data from clinical and basic research suggested that the integrity of the intestinal barrier might be a key determinant in translating autoimmunity to inflammation, making intestinal permeability a potential marker or a target for future therapies.Objectives:To analyse the available data on intestinal permeability in SpA patients and the effects of drugs such as non-steroidal anti-inflammatory drugs (NSAIDs) on intestinal permeability.Methods:A systematic review was conducted. Without date restriction, the following databases were searched through September 1, 2020: Medline, Embase and Cochrane. Studies with patients with SpA assessing the intestinal permeability were selected. Some of the included studies have assessed the effect of NSAIDs on intestinal permeability.Results:A total of 12 studies were included in the final analysis. The 12 studies involved a total of 268 SpA patients, including 240 ankylosing spondylitis (AS). Among the studies included, four studies used the lactulose/mannitol test, four studies used the 51Cr-ethylenediaminetetraacetic test and two studies used the polyethylene glycols test. Nine of the 12 studies reported increased intestinal permeability regardless on the method used for intestinal permeability evaluation. Four studies evaluated the link between disease activity, assessed by CRP and ESR levels, and intestinal permeability and showed no correlation between increased intestinal permeability and markers of disease activity in AS patients. As regards the effects of NSAIDs on intestinal permeability, data are controversial. Two studies, including one evaluating indomethacin, did not show any influence of NSAIDs in AS patients, one study showed an increase in intestinal permeability under NSAIDs in only 60% of the patients, another study reported increased intestinal permeability. When comparing the effect of NSAIDs in patients with AS to healthy subjects, one study reported a comparable NSAIDs-induced increase in intestinal permeability in both groups.Conclusion:The results of our review suggest that increased intestinal permeability is present in SpA patients even in the absence of NSAIDs use and regardless of the method used to assess intestinal permeability. The effects of NSAIDs on intestinal permeability in SpA patients is more controversial and further studies are needed to clarify them.Disclosure of Interests:None declared

Permeability evaluation of gemcitabine-CPP6 conjugates in Caco-2 cells

Cancer is one of the most alarming diseases due to its high mortality and still increasing incidence rate. Currently available treatments for this condition present several shortcomings and new options are continuously being developed and evaluated, aiming at increasing the overall treatment efficiency and reducing associated adverse side effects. Gemcitabine has proven activity and is used in chemotherapy. However, its therapeutic efficiency is limited by its low bioavailability as a result of rapid enzymatic inactivation. Additionally, tumor cells often develop drug resistance after initial tumor regression related to transporter deficiency. We have previously developed three gemcitabine conjugates with cell-penetrating hexapeptides (CPP6) to facilitate intracellular delivery of this drug while also preventing enzymatic deamination. The bioactivity of these new prodrugs was evaluated in different cell lines and showed promising results. Here, we assessed the absorption and permeability across Caco-2 monolayers of these conjugates in comparison with gemcitabine and the respective isolated cell-penetrating peptides (CPPs). CPP6-2 (KLPVMW) and respective Gem-CPP6-2 conjugate showed the highest permeability in Caco-2 cells.