N-feruloylserotonin in preventive combination therapy with methotrexate reduced inflammation in adjuvant arthritis.

Many of disease-modifying anti-rheumatic drugs often have side effects at high doses and/or during long-term administration. Increased efficacy without increased toxicity is expected for combination therapy of rheumatoid arthritis (RA). The aim of the study was to examine the effect of N-feruloylserotonin (N-f-5HT) and methotrexate (MTX) in monotherapy and in combination therapy on disease progression and inflammation in arthritic rats. Adjuvant arthritis was induced by intradermal injection of Mycobacterium butyricum in incomplete Freund's adjuvant in Lewis rats. The experiment included healthy animals, arthritic animals without any drug administration, arthritic animals with administration of N-f-5HT in the oral daily dose of 15 mg/kg b.w., arthritic animals with administration of MTX in the oral dose of 0.3 mg/kg b.w. twice a week and arthritic animals treated with the combination of N-f-5HT and MTX. N-f-5HT in monotherapy reduced only activation of NF-jB and did not have any significant effect on other parameters monitored. Low-dose treatment of MTX decreased the level of IL-1b and MCP-1 on day 14 and activation of NF-jB in liver without significant effect on other parameters. N-f-5HT and MTX combination showed both the anti-arthritic (hind paw volume and arthritic score) and anti-inflammatory effect (plasmatic levels of IL-1b, IL-17, MCP-1, CRP, and activation of NF-jB in liver). In combination with MTX, N-f-5HT markedly potentiated the therapeutic effect of MTX low dose, which resulted in significant improvement of all parameters measured. The findings showed that the combination therapy simultaneously decreased multiple markers of inflammation, a result crucial for future therapy of RA

Occurrence of perfluoroalkyl substances (PFASs) in various food items of animal origin collected in four European countries

This study summarises the results of the levels of 21 perfluoroalkyl substances (PFASs) in 50 selected pooled samples representing 15 food commodities with the special focus on those of animal origin, as meat, seafood, fish, milk, dairy products and hen eggs, which are commonly consumed in various European markets, e.g. Czech, Italian, Belgian and Norwegian. A new, rapid sample preparation approach based on the QuEChERS extraction procedure was applied. Ultra-performance liquid chromatography (UHPLC) coupled to tandem mass spectrometry (MS/MS) employing electrospray ionisation (ESI) in negative mode was used for the quantification of target analytes. Method quantification limits (MQLs) were in the range of 1-10 ng kg−1 (ng l−1) for fish, meat, hen eggs, cheese and milk, and in the range of 2.5-125 ng kg−1 for butter. Only 16 of the group of 21 PFASs were found in at least one analysed sample. From 16 PFASs, perfluorooctane sulfonate (PFOS) was the most frequently detected analyte present in approximately 50% of samples (in the range of 0.98-2600 ng kg−1). PFCAs with C8-C14 carbon chain were presented in approximately 20% of samples. The concentration ranges of individual compounds in the respective groups of PFASs were: 2.33-76.3 ng kg−1 for PFSAs (without PFOS), 4.99-961 ng kg−1 for PFCAs, 10.6-95.4 ng kg−1 for PFPAs, and 1.61-519 ng kg−1 for FOSA. The contamination level in the analysed food commodities decreased in the following order: seafood > pig/bovine liver >> freshwater/marine fish > hen egg > meat >> butter. When comparing the total contamination and profiles of PFASs in food commodities that originated from various sampling countries, differences were identified, and the contents decreased as follows: Belgium >> Norway, Italy > Czech Republic