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Marta Szandruk-Bender,1 Anna Merwid-Ląd,1 Benita Wiatrak,1 Maciej Danielewski,1 Stanisław Dzimira,2 Danuta Szkudlarek,3 Łukasz Szczukowski,4 Piotr Świątek,4 Adam Szeląg1 1Department of Pharmacology, Wroclaw Medical University, Wrocław, Poland; 2Department of Pathology, Wroclaw University of Environmental and Life Sciences, Wrocław, Poland; 3Foundation of the Wroclaw Medical University, Wroclaw Medical University, Wrocław, Poland; 4Department of Chemistry of Drugs, Wroclaw Medical University, Wrocław, PolandCorrespondence: Marta Szandruk-BenderDepartment of Pharmacology, Wroclaw Medical University, Mikulicza-Radeckiego 2, Wrocław, 50-345, PolandTel +48717841438Fax +48717840094Email marta.szandruk@umed.wroc.plBackground and Purpose: Due to the risk of gastrointestinal damage and various tissue toxicity associated with non-steroidal anti-inflammatory drugs (NSAIDs) use, investigating new anti-inflammatory agents with efficacy comparable to that of NSAIDs but reduced toxicity is still a major challenge and a clinical need. Based on our previous study, new 1,3,4-oxadiazole derivatives of pyrrolo[3,4-d]pyridazinone, especially 6-butyl-3,5,7-trimethyl-1-[[4-[[4-(4-nitrophenyl)piperazin-1-yl]methyl]-5-thioxo-1,3,4-oxadiazol-2-yl]methoxy]pyrrolo[3,4-d]pyridazin-4-one and 6-butyl-1-[[4-[[4-(4-chlorophenyl)-4-hydroxy-1-piperidyl]methyl]-2-thioxo-1,3,4-oxadiazol-5-yl]methoxy]-3,5,7-trimethyl-pyrrolo[3,4-d]pyridazin-4-one (hereafter referred to as the compounds 10b and 13b, respectively) seem to be promising anti-inflammatory agents. This study aimed to elucidate the effects of these two new derivatives on the course of experimental rat inflammation, liver and kidney function, and gastric mucosa.Methods: The anti-inflammatory effect of compounds 10b and 13b was evaluated using the carrageenan-induced paw edema test in rats. The increase in paw volume (paw edema), prostaglandin E2 (PGE2), tumor necrosis factor-α (TNF-α) and myeloperoxidase (MPO) levels, histological alterations, and inflammatory cell infiltration in paw tissue were determined. Serum alanine transaminase (ALT) and aspartate transaminase (AST) activities, serum urea and creatinine levels, as well as changes in gastric mucosa, were measured as indicators of hepatic, renal, and gastric toxicity.Results: Pretreatment with both novel derivatives at 10 mg/kg and 20 mg/kg doses reduced paw edema, counteracted the increased PGE2 and TNF-α levels, reduced the influx of inflammatory cells, and decreased histopathological alterations in paw tissue. Compound 13b at a dose of 20 mg/kg was more effective than indomethacin in reversing the increased TNF-α levels and reducing the influx of inflammatory cells. Only compound 13b at all studied doses (5, 10, or 20 mg/kg) counteracted the increased MPO level in paw tissue. Both compounds neither caused alterations in ALT, AST, urea, creatinine parameters nor gastric mucosal lesions.Conclusion: New compounds exert an anti-inflammatory effect, presumably via inhibiting inflammatory mediators release and inflammatory cell infiltration. Moreover, both possess a more favorable benefit–risk profile than indomethacin, especially compound 13b.Keywords: carrageenan, anti-inflammatory agents, pyrrolo[3,4-d]pyridazinone, 1,3,4-oxadiazole, inflammatory mediators, toxicity

The oxidation behavior of five different high-entropy alloys from the Al–Co–Cr–Fe–Ni metallic system, namely Alx(CoCrFeNi)100-x (x = 0; 3; 6; 9; 12), was studied under thermal-cycling conditions, at 1273 K in air atmosphere. The choice of selected compositions allowed for covering the chromia-to-alumina former transition, as well as the transition from the FCC single-phase solid solution structure to multiphase alloys with Al-enriched B2-structured constituent. The measurements were taken for 500 cycles (1 cycle - 1 h of heating, 20 min of cooling). The results indicate a profound influence of the thermal-cycling conditions on the oxidation products, with extremely complex scale structures and extensive internal oxidation and nitridation zones, as well as severe spallation of the oxide scale in most cases, showing the limited usefulness of these alloys for high-temperature applications at the current stage of their development. [ABSTRACT FROM AUTHOR]

Self-consistent model of generation, interaction, and annihilation of point defects in the gradient of oscillating stresses is presented. This model describes the recently suggested method of severe plastic deformation by combination of pressure and oscillating rotations of the die along the billet axis (KoBo process). Model provides the existence of distinct zone of reduced viscosity with sharply increased concentration of point defects. This zone provides the high extrusion velocity. Presented model confirms that the Severe Plastic Deformation (SPD) in KoBo may be treated as non-equilibrium phase transition of abrupt drop of viscosity in rather well defined spatial zone. In this very zone, an intensive lateral rotational movement proceeds together with generation of point defects which in self-organized manner make rotation possible by the decrease of viscosity. The special properties of material under KoBo version of SPD can be described without using the concepts of nonequilibrium grain boundaries, ballistic jumps and amorphization. The model can be extended to include different SPD processes. [ABSTRACT FROM AUTHOR]

We present the first experimental results of the growth of Cu6Sn5 and Cu3Sn under an external force field – during the sedimentation process. The results are compared with the proposed model under the combined influence of the Kirkendall effect, backstress and sedimentation. It is shown that Cu3Sn consumes the preformed Cu6Sn5 phase during sedimentation under a strong gravitational field of 779,000 G at 200 °C.