Novel Bioactivation Pathway of Benzbromarone Mediated by Cytochrome P450

ABSTRACT Benzbromarone (BBR) is a hepatotoxic drug, but the detailed mechanism of its toxicity remains unknown. We identified 2,6-dibromohydroquinone (DBH) and mono-debrominated catechol (2-ethyl-3-(3-bromo-4,5-dihydroxybenzoyl)benzofuran; CAT) as novel metabolites of BBR in rat and human liver microsomal systems by comparison with chemically synthesized authentic compounds, and we also elucidated that DBH is formed by cytochrome P450 2C9 and that CAT is formed mainly by CYP1A1, 2D6, 2E1, and 3A4. Furthermore, CAT, DBH, and the oxidized form of DBH are highly cytotoxic in HepG2 compared with BBR. Taken together, our data demonstrate that DBH, a novel reactive metabolite, may be relevant to BBR-induced hepatotoxicity

digital design and wooden architecture for arte sella land art park

Digital design is increasingly sinking the construction sector, shaping and validating architecture according to various criteria and introducing the wood industry to the 4.0 approach. Within the study entitled "Architecture at Arte Sella", parametric design, structural validations and CNC procedures are exploited to help define, control and assess several architectural woodworks, created with famous designers. This contribution describes the design and construction experiences of Atsushi Kitagawara (2017) and Kengo Kuma (2018–2019), the two masterpieces installed in the land art park of Arte Sella (Trento, Italy) and developed, thanks to the Politecnico di Milano team, from design to mock-ups, testing and construction

Wooden Byobu. From Architectural Façade to Sculpture

The Japanese Pavilion at EXPO Milano 2015, designed by Atsushi Kitagawara, has been visited by millions of people with great success, especially for its stunning wooden façade. Its naked structure is defined by only one element, a 12 × 12 cm section, whose larch came from Fukushima region, to show the health of the forest after the terrible Tsunami. The façade was conceived with studs, connected without any screws or nails, thanks to the “compressive-tension” effect, whose concept interprets old Japanese wooden-based techniques of constructions and even handcrafts of complex wooden toys. Analogic mock-ups and parametric models have defined the entire design phase, leading to a simple form at the end of a complex research path. The wooden structure was, then, elaborated and produced through CNC processes, built for EXPO Milano 2015, and dismantled after the event. A new life of this concept is becoming an art object: the Byobu. This is a traditional separating screen in Japanese houses, something that creates space and multiple possibilities. Thus, the structural concept of EXPO Milano 2015 turns into several variations for different places: University Byobu at Politecnico di Milano, Urban Byobu at Farm Cultural Park in Sicily, Forest Byobu at Arte Sella, near Trento, and finally Museum Byobu—Kigumi Infinity at Mori Art Museum in Tokyo. All these examples leave a memory of a stunning structure, conceived to be temporary for EXPO Milano 2015, now visible in several places between Italy and Japan