Inhibitors of hyaluronan export from hops prevent osteoarthritic reactions

Scope: An early reaction in osteoarthritic chondrocytes is hyaluronan overproduction followed by proteoglycan loss and collagen degradation. We recently found that hyaluronan is exported by the ATP‐binding cassette transporter multidrug resistance associated protein 5 (MRP5) in competition with cGMP and that some phosphodiesterase 5 inhibitors also inhibited hyaluronan export. These inhibitors also prevented osteoarthritic reactions in cartilage. In an effort to identify the improved inhibitors directed primarily toward MRP5, we analyzed the flavonoids Methods and results: Prenylflavonoids from hop xanthohumol, isoxanthohumol and 8‐prenylnaringenin inhibited MRP5 export at lower concentrations than phosphodiesterase 5 activity. They were analyzed for their effect on IL‐induced osteoarthritic reactions in bovine chondrocytes. Xanthohumol was the superior compound to inhibit hyaluronan export, as well as proteoglycan and collagen loss. It also prevented the shedding of metalloproteases into the culture medium. It directly inhibited MRP5, because it reduced the export of the MRP5 substrate fluorescein immediately and did not influence the hyaluronan synthase activity. Conclusions: Xanthohumol may be a natural compound to prevent hyaluronan overproduction and subsequent reactions in osteoarthritis.     

Efficient shape optimization for certain and uncertain aerodynamic design

In this paper, we present novel developments in aerodynamic shape optimization based on shape calculus as well as the proper treatment of aleatoric uncertainties in the field of aerodynamic design.     

In Vivo and In Vitro Degradation Behavior of Magnesium Alloys as Biomaterials

The corrosion behavior of pure Mg,AZ31,and AZ91D were evaluated in various in vitro and in vivo environments to investigate the potential application of these metals as biodegradable implant materials.DC polarization tests and immersion tests were performed in different simulated body solutions,such as distilled(DI) water,simulated body fluid(SBF) and phosphate buffered solution(PBS).Mg/Mg alloys were also implanted in different places in a mouse for in vivo weight loss and biocompatibility investigations.The in vivo subcutis bio-corrosion rate was lower than the corrosion rate for all of the in vitro simulated corrosive environments.The Mg/Mg alloys were biocompatible based on histology results for the liver,heart,kidney,skin and lung of the mouse during the two months implantation.Optical microscopy and scanning electron microscopy were carried out to investigate the morphology and topography of Mg/Mg alloys after immersion testing and implantation to understand the corrosion mechanisms.     

Minimierung der Umbauzeiten bei Stahlwerksmodernisierungen am Beispiel eines Stranggießanlagen-Umbaues

In November 2000 the Belgian stainless steel producer UGINE & ALZ Belgium nv, a company of the Arcelor Group, awarded VAI a contract for the upgrading and expansion of their steelmaking plant. The overall project included the revamping and supply of new equipment and systems for the steelmaking, continuous casting and environmental protection facilities. An essential part of this ambitious modernization program was the upgrading and expansion of the existing single-strand slab caster, with an output of 600 000 t/a, to a combined single- or twin-strand slab caster with a nominal production capacity of 1.2 million tons — the world’s largest stainless steel slab caster. All upgrading and installation activities had to be carried out within an extremely tight caster shut-down period of 21 days only in order to minimize production losses. This paper discusses the innovative project management solutions implemented in combination with extensive preassembly activities and workshop testing to assure the successful outcome of this project.     

Bicyclische Oxalamidine – Bausteine für hochsubstituierte 2,2′-Bipyridine und Benzolderivate

Bicyclic Oxalic Amidines as Building Blocks for Highly Substituted 2,2′-Bipyridines and Benzene Derivatives The bis-imidoylchlorides 1 derived from oxalic acid exhibit a high regio- and chemoselectivity. As in the case of 2-picolylamine 2 the acylation with oxalyl chloride furnished the expected open chained oxalic diamides 3a while the imidoylchlorides 1 yield exclusively the new pyrido[1,2-a]-pyrazines 4 . These heterocycles represent readily crystallisable and orange-red coloured compounds with a mesomeric dipolar aromatic substructure. The synthetic value of 4 is based on their easy transformation into highly substituted arenes and hetarenes. Thus, electron deficient dienophiles as dimethyl acetylenedicarboxylate lead to the bipyridines 6 via Hetero-Diels-Alder-Reaction and subsequent 1,5-hydrogen shift. In a complex reaction the derivatives of maleic acid 7a – c yield the bipyridines of type 9 while the new hexasubstituted arenes 10 can be isolated under anaerobic conditions and with an excess of dienophilic component. A x-ray structural determination of 10b shows an alternation of bond lenghts in the benzene ring. This can be considered as a distinct disturbance of aromaticity caused by the arrangement of substituents.     

Radikalreaktionen an N-Heterocyclen. XI [1] Reaktionen von 3-Methyl-pyrazolin-5-onen mit Phenoxyl-Radikalen

Free Radical Reactions of N-Heterocyclic Compounds. XI. Reaction of 3-Methyl-pyrazolin-5-ones with Phenoxy Radicals Pyrazolin-5-ones ( 3a–i ) were oxidized with 2,4,6-trisubstituted phenoxy radicals ( 2a–d ) to the corresponding radicals ( 4a–i ), which dimerised or combined with phenoxy radical ( 2a ) depending on the R¹- and R⁴-substituents in ( 3 ). In the case of 3-methyl-1-phenyl-pyrazolin-5-one ( 3f ) the primary radical combination products were not found, but the corresponding quinone methide ( 17 ) and the o-phenol derivative ( 18 ) were isolated. Products and yields have been investigated as a function of mol ratio substrate: oxidant and solvent. The radical combination products ( 7–10 ) could de-tertbutylated in the presence of aluminium chloride or in the presence of trifluoroarcetic acid, forming heterocyclic substituted phenols ( 21 ) and ( 22 ).     

Azoperoxide. VI. Selektive Spaltungen von β-Azo-acylperoxiden

Azoperoxides. VI. Selective Decomposition of β-Azoacylperoxides The selective decomposition of the O O-Groups in the azoperoxides 1 and 2 is possible by reaction with dimethylaniline at 35°C. Rate constants were measured and the decomposition products were analyzed. Intermediates are azoalkyl radicals. The radical yield of the amine induced decomposition of 2 in ethylbenzene is 8.2% at 35°C. UV irradiation of the azoperoxides 1 and 2 at 20°C in ethylbenzene results in a quantitative and selective decomposition of the azo groups. Intermediates are C-radicals with intact peroxide groups. The reaction of 1 and 2 with triethylstannane yields reduction products of the O O-groups and the NN-groups, respectively.     

Scrubbing carbon dioxide prevents overestimation of insect mortality in long-duration static phosphine toxicity assays

Exposing insects to toxicants such as phosphine (PH₃) in sealed chambers is a common procedure in fumigant efficacy testing. During long exposures, carbon dioxide (CO₂) produced by metabolic processes of fed insects may accumulate in the vessel. As CO₂ enhances the toxicity of several fumigants, concomitant exposure of fumigant and CO₂ may lead to erroneous measurements of insect mortality and thus fumigant toxicity. In this study, the effect of a CO₂ scrubber such as soda lime (a solid formulation of wet hydroxides of calcium, sodium and potassium) or periodic flushing of the headspace, on insect mortality in static PH₃ toxicity assays was compared with an “unscrubbed” (no intervention) treatment. Soda lime was highly effective in removing CO₂ from the headspace of sealed chambers, without measurable loss of PH₃. Mortality of Sitophilus oryzae (L.) adults treated with phosphine in chambers scrubbed with soda lime or flushed (opened) daily was considerably lower than in unscrubbed chambers. Twenty grams of soda lime per litre of exposure chamber is recommended to obtain accurate static fumigant mortality results.