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Kynurenic acid (KynA), a broad spectrum antagonist of excitatory amino acid receptors, may serve as a protective agent in neurological disorders. The potential anti-inflammatory effect of KynA in human leukocytes has not been characterized. The aim of this study was to compare the effects of KynA with those of a new analogue, 2-(2-N,N-dimethylaminoethylamine-1-carbonyl)-1H-quinolin-4-one hydrochloride on tumour necrosis factor-α (TNF-α) production and high mobility group box protein 1 (HMGB1) secretion. The effects of KynA on granulocyte activation were investigated via the secretion of human neutrophil peptide 1-3 (HNP1-3). Peripheral blood mononuclear cells and granulocytes or CD14 positive monocytes were applied as effector cells, or whole blood cultures were used. TNF-α, HMGB1 and HNP1-3 concentrations were determined by ELISA, TNF-α and HNP1-3 mRNA expressions were quantified by reverse transcription PCR. KynA attenuated the TNF-α production of human mononuclear cells activated by heat-inactivated Staphylococcus aureus, inhibiting TNF-α production at the transcription level. Furthermore, KynA diminished HMGB1 secretion by U 937 monocytic cells and by peripheral blood monocytes. KynA inhibited the HNP1-3 secretion in whole blood and in granulocyte cultures. The suppressive effect of the KynA analogue was more potent than that of an equimolar concentration KynA in TNF-α, HMGB1 and HNP1-3 inhibition. These results suggest that the new KynA analogue has a more potent immunoregulatory effect than KynA on human mononuclear cells, monocytes and granulocytes and indicate the potential benefits of further exploration of its uses in human inflammatory disease.

Variations in the serine protease 1 (PRSS1) gene encoding human cationic trypsinogen have been conclusively associated with autosomal dominant hereditary pancreatitis and sporadic nonalcoholic chronic pancreatitis. Most high-penetrance PRSS1 variants increase intrapancreatic trypsin activity by stimulating trypsinogen autoactivation and/or by inhibiting chymotrypsin C-dependent trypsinogen degradation. Alternatively, some PRSS1 variants can cause trypsinogen misfolding, which results in intracellular retention and degradation with consequent endoplasmic reticulum stress. However, not all PRSS1 variants are pathogenic, and clinical relevance of rare variants is often difficult to ascertain. Here we review the PRSS1 variants published since 1996 and discuss their functional properties and role in chronic pancreatitis.

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Sunlight penetration through the water column is controlled by the amount and kind of materials dissolved and suspended in the water. Understanding UV penetration in its complexity is essential for the prediction of the impact of UV radiation on aquatic ecosystems. However, only limited data are available on the penetration of UVR into shallow waters rich in inorganic suspended solids and chromophoric dissolved organic matter (CDOM). The same is true for the specific attenuation coefficients of light-absorbing components at the UV waveband. This study analyses the role of CDOM, algal-free suspended solids and algae in the formation of underwater UVR and PAR climate in 30 water bodies from clear gravel pit lakes trough the shallow Lake Balaton to turbid soda pans. Irradiance-depth profiles were obtained at 305, 313, 320 nm (UV-B), 340, 380, 395 nm (UV-A) and 400-700 nm (PAR) with a Biospherical PUV-2500 radiometer. Vertical attenuation coefficients (K d ) were calculated. Water samples were taken for the laboratory measurement of the concentration of light-absorbing components: algae as chlorophyll a (CHL), chromophoric dissolved organic matter as colour (CDOM), and algalfree suspended solids (TSS-Alg) parallel with the in situ light measurements. Specific attenuation coefficient values were calculated by multiple regression analysis (n = 140). The obtained specific UV attenuation coefficient values of CHL, CDOM and TSSAlg made it possible to establish light attenuation at different wavelengths based on the knowledge of the concentration of these light-absorbing components.

Background: Hereditary pancreatitis-associated mutations alter regulation of trypsinogen activation by chymotrypsin C. Results: Activation of mouse trypsinogens T8 and T9 is inhibited by chymotrypsin C-mediated cleavage of the autolysis loop. Conclusion: Chymotrypsin C regulates activation of human and mouse trypsinogens by different mechanisms. Significance: Introduction of human pancreatitis-associated mutations into mouse trypsinogens will not recapitulate the pathogenic biochemical effects.

The EASY prediction score is a practical tool for identifying patients at a greater risk for severe acute pancreatitis shortly after hospital admission. • The explanation of the impact of features on the prediction helps physicians understand the decision of the machine learning model.• The easy-to-use web application is available for clinicians and contributes to the improvement of the model.

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