Aims/hypothesis: The 11β-hydroxysteroid dehydrogenase type-1 inhibitor BVT.2733 lowers blood glucose and insulin in mutant mouse models of obesity and diabetes. Its effects on energy balance and body composition, and their contribution to improved glucose homeostasis have received little attention. Materials and methods: BVT.2733 (100 mg/kg, orally) was given twice daily to lean and diet-induced obese mice for 16 or 17 days. A group of obese mice was pair-fed to the amounts consumed by BVT.2733-treated mice. Results: In both obese and lean mice, BVT.2733 reduced food intake and weight gain, but increased water intake. Pair-feeding caused almost as great a decrease in body weight as BVT.2733. Energy expenditure was 38±8% higher in the BVT.2733-treated obese mice than in the pair-fed mice. Terminal plasma corticosterone was raised, lean body weight reduced and percentage fat unchanged in the pairfed mice (control, 47.8±2.6%; pair-fed, 47.1±1.9%), whereas BVT.2733 did not reduce lean mass, but did reduce percentage fat (40.9±2.0%). BVT.2733 but not pairfeeding reduced both the glucose tolerance AUC and the plasma insulin concentration 30 min after giving glucose. Conclusions/interpretation: BVT.2733 reduced food intake but prevented a concomitant reduction in lean body mass and energy expenditure. The latter effects may have contributed to improved glucose tolerance.

A rare case of multiple idiopathic root resorption (MIRR) involving 5 adjacent anterior and posterior teeth is presented and the pathogenesis discussed. The proposition is made that MIRR results from microbiologically-induced osteoclast activity facilitated by prior osteoblast activation.

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The lead isotopic composition of various sections (crown, crown base, root) of teeth was determined in specimens collected from 19th century skulls preserved in museum collections and, upon extraction or exfoliation, from humans of known ages residing in Scotland in the 1990s. For most 20th century samples, calculation of accurate crown-complete or root-complete dates of tooth formation ranging from the 1920s to the 1990s enabled comparison of (206)Pb/(207)Pb ratios for teeth sections (crown base root) with corresponding decadally averaged data for archival herbarium Sphagnum moss samples. This showed that the teeth sections had been significantly influenced by incorporation of non-contemporaneous (more recent) lead subsequent to the time of tooth formation, most probably via continuous uptake by dentine. This finding confirmed that separation of enamel from dentine is necessary for the potential of teeth sections as historical biomonitors of environmental (and dietary) lead exposure at the time of tooth formation to be realised. Nevertheless, the mean 19th century value of 1.172+/-0.007 for the (206)Pb/(207)Pb ratio in teeth was very similar to the corresponding mean value of 1.173+/-0.004 for 19th century archival moss, although relative contributions from environmental sources - whether direct, by inhalation/ingestion of dust contaminated by local lead smelting ((206)Pb/(207)Pb~1.17) and coal combustion ((206)Pb/(207)Pb~1.18) emissions, or indirect, through ingestion of similarly contaminated food - and drinking/cooking water contaminated by lead pipes of local origin, cannot readily be determined. In the 20th century, however, the much lower values of the (206)Pb/(207)Pb ratio (range 1.100-1.166, mean 1.126+/-0.013, median 1.124) for the teeth collected from various age groups in the 1990s reflect the significant influence of imported Australian lead of lower (206)Pb/(207)Pb ratio (~1.04) and released to the environment most notably through car-exhaust emissions arising from the use of alkyl lead additives ((206)Pb/(207)Pb~1.06-1.09) in petrol in the U.K. from ca. 1930 until the end of the 20th century.

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