Collection and X-ray microanalysis of airway surface liquid in the mouse using ion exchange beads

The airway surface liquid (ASL) is a thin layer of liquid covering the airway epithelium. The ionic composition of the ASL is assumed to be important for airway function and may be altered in diseases such as cystic fibrosis and exercise-induced asthma. A method for collection of ASL is presented in which the fluid is collected using small dextran ion-exchange beads. The beads are equilibrated with the ASL in a humidity chamber, collected under silicon oil, dried and analyzed by X-ray microanalysis. Analysis of standard beads prepared by exposure to different salt solutions shows that linear calibration lines can be obtained, but that beads absorb different elements to a different extent. The results show that the ASL in mice is hypotonic, and that the mucus component of the ASL has an elemental composition that is different from that of the periciliary fluid.     

The acrylamide content of smokeless tobacco products

Background

There is considerable interest from a regulatory and public health perspective in harmful and potentially harmful constituents in tobacco products, including smokeless tobacco products (STPs). A wide range of commercial STPs from the US and Sweden, representing 80–90 % of the 2010 market share for all the major STP categories in these two countries, were analysed for the IARC Group 2A carcinogen acrylamide. These STPs comprised the following styles: Swedish loose and portion snus, US snus, chewing tobacco, moist snuff, dry snuff, soft pellet, hard pellet and plug.

Results

Acrylamide was detected in all the products tested and quantified in all but one product. Concentrations ranged from 62 to 666 ng/g wet weight basis (WWB). The average levels of acrylamide (WWB) by type of STP were not significantly different (p > 0.05) except for US snus which had, on average, greater levels but with a very wide range of individual levels according to the manufacturer. Acrylamide levels in STPs were significantly and positively correlated with pH, but not with levels of either reducing sugars or ammonia nitrogen. Levels of acrylamide increased by sixfold or more (on a dry weight basis) during manufacture of a snus sample and then decreased during subsequent storage for up to 22 weeks. Acrylamide generation in tobacco generally appears to occur at lower temperatures, but longer time scales than found with food production.

Conclusions

Acrylamide is a common contaminant of STPs, formed through heat treatment of tobacco. Our data show that exposure to acrylamide from consumption of STPs is small compared with exposure from food consumption or cigarette smoking.

     

The exocyclic functionalisation of bis(thiosemicarbazonate) complexes of zinc and copper: the synthesis of monomeric and dimeric species

This paper reports the synthesis of bimetallic zinc thiosemicarbazone complexes with rigid aromatic linkers, using either 1,3- or 1,4- benzenediamines or 1,3- or 1,4- benzenedialdehydes as the basis of the linking groups. Non-rigid aliphatic diamines and dialdehydes were also used to link the zinc chelating units. Reaction of a bis(thiosemicarbazone) with a pendant NHNH(2) group with monoaldehydes or ketones gives a range of monomeric complexes with exocylic imine groups bearing a range of substituents. The zinc complexes can be quantitatively and rapidly transmetallated to the corresponding copper complexes and this route or direct reaction with the free ligand can be used to radiolabel the monomeric species with (64)Cu. In vivo and in vitro studies of one of the (64)Cu imine complexes shows substantial hypoxic selectivity and high tumour uptake in a murine model.     

Mathematical Dimensions of Students' Use of Proportional Reasoning In High School Physics

This study examines the mathematical processes used by students when solving physics tasks requiring proportional reasoning. The study investigates students' understanding and explanations of their mathematical processes. A qualitative and interpretive case study was conducted with 6 students from a coeducational urban high school for 5 months. Students were engaged with some high school physics tasks requiring proportional reasoning, during which a hermeneutic dialectic design was used to investigate their processes, understandings, and difficulties. Research techniques such as interviews, dialectical discourses, journal dialogue, and video and audio recordings were employed to generate, analyze, and interpret data. Results of the study indicate that the students employed mathematical proportional reasoning patterns and algorithms which they could not explain. Students also had difficulties translating physics tasks into mathematical statements, symbols, and relations. Students could not perform mathematical operations that were not directly obvious from the physics tasks, and some had difficulty with division. Students did not have adequate understanding of the mathematical processes involved in proportional reasoning.     

Manganese(III)-mediated radical cyclisations for the (Z)-selective synthesis of exo-alkylidene pyrrolidinones and pyrrolidines

The cyclisation of alkynyl amido- and amino-malonates in the presence of manganese(III) acetate gives exo-alkylidene pyrrolidinones and pyrrolidines with a preference for the (Z)-alkene product isomer.     

N3-alkylation during formation of quinazolin-4-ones from condensation of anthranilamides and orthoamides

Dimethylformamide dimethylacetal (DMFDMA) is widely used as a source of electrophilic one-carbon units at the formate oxidation level; however, electrophilic methylation with this reagent is previously unreported. Reaction of anthranilamide with DMFDMA at 150 °C for short periods gives mainly quinazolin-4-one. However, prolonged reaction with dimethylformamide di(primary-alkyl)acetals leads to subsequent alkylation at N(3). 3-Substituted anthranilamides give 8-substituted 3-alkylquinazolin-4-ones. Condensation of anthranilamides with dimethylacetamide dimethylacetal provides 2,3-dimethylquinazolin-4-ones. In these reactions, the source of the N(3)-alkyl group is the O-alkyl group of the orthoamides. By contrast, reaction with the more sterically crowded dimethylformamide di(isopropyl)acetal diverts the alkylation to the oxygen, giving 4-isopropoxyquinazolines, along with N(3)-methylquinazolin-4-ones where the methyl is derived from N-Me of the orthoamides. Reaction of anthranilamide with the highly sterically demanding dimethylformamide di(t-butyl)acetal gives largely quinazolin-4-one, whereas dimethylformamide di(neopentyl)acetal forms a mixture of quinazolin-4-one and N(3)-methylquinazolin-4-one. The observations are rationalised in terms of formation of intermediate cationic electrophiles (alkoxymethylidene-N,N-dimethylammonium) by thermal elimination of the corresponding alkoxide from the orthoamides. These are the first observations of orthoamides as direct alkylating agents.