Excess dietary iodine intake in long-term African refugees

Abstract Objective To assess the iodine status of long-term refugees dependent on international food aid and humanitarian assistance. Design A series of cross-sectional two-stage cluster or systematic random sample surveys which assessed urinary iodine excretion and the prevalence of visible goitre. Salt samples were also collected and tested for iodine content by titration. Setting Six refugee camps in East, North and Southern Africa. Subjects Male and female adolescents aged 10-19 years. Main results The median urinary iodine concentration (UIC) ranged from 254 to 1200 μg l−1 and in five of the camps exceeded the recommended maximum limit of 300 μg l−1, indicating excessive iodine intake. Visible goitre was assessed in four surveys where it ranged from 0.0 to 7.1%. The camp with the highest UIC also had the highest prevalence of visible goitre. The iodine concentrations in 11 salt samples from three camps were measured by titration and six of these exceeded the production-level concentration of 20 to 40 ppm recommended by the World Health Organization (WHO), but were all less than 100 ppm. Conclusions Excessive consumption of iodine is occurring in most of the surveyed populations. Urgent revision of the level of salt iodisation is required to meet current WHO recommendations. However, the full cause of excessive iodine excretion remains unknown and further investigation is required urgently to identify the cause, assess any health impact and identify remedial actio

Electrophilic additions to functionalised alkenes : the chemistry and synthesis of heterocyclic compounds

The electrophilic addition of organosulphur compounds to alkenes is reviewed. The oxidative electrophilic addition of diphenyl disulphide [using manganese (III) acetate as the oxidant] to a series of alkenes carrying a range of remote nucleophilic groups is described. For example the alkenes investigated carry either amide, urea, thiourea, carbamic acid, carbamimidothioic acid, carbondithioic acid, carbontrithioic acid, guanidine, and sulphonamide functionalities. On the addition of diphenyl disulphide these alkenes afford a number of novel cyclic and acyclic sulphur substituted compounds. A review is made of the literature background to the electrophilic addition-cyclisation reaction of iodine with alkenes carrying remote nucleophiles. A number of novel iodosubstituted heterocyclic compounds are efficiently synthesised via the addition of iodine to alkenes carrying either thiourea, carbamimidothioic acid, carbontrithioic acid, and guanidine functionalities. The principle factors determining the mode of these cyclisations are discussed. Dehydroiodination of these compounds affords a variety of novel unsaturated heterocycles. A route through to 5-methylenedihydrothiaxolamines, 6-methylenedihydrothiaxinamines, and 6-methylenetetrahydropyrimidines, and related compounds, having synthetic potential as both nucleophiles, and electrophiles is established. Related reactions with anaolgous methylene lactones, methylenethiaxoles, methylenedihydro-oxazoles, and methylene cyclic carbonates are noted. Further elaboration of the iodosubstituted heterocycles by the substitution of iodine with carbon, nitrogen, oxygen, and sulphur nucleophiles is reported. Examples are given of carbon-carbon bond formation, via free radical substitution reactions, using organotin chemistry.</p

Recombinant sclerostin inhibits bone formation in vitro and in a mouse model of sclerosteosis

Background: Sclerosteosis, a severe autosomal recessive sclerosing skeletal dysplasia characterised by excessive bone formation, is caused by absence of sclerostin, a negative regulator of bone formation that binds LRP5/6 Wnt co-receptors. Current treatment is limited to surgical management of symptoms arising from bone overgrowth. This study investigated the effectiveness of sclerostin replacement therapy in a mouse model of sclerosteosis. Methods: Recombinant wild type mouse sclerostin (mScl) and novel mScl fusion proteins containing a C-terminal human Fc (mScl hFc), or C-terminal human Fc with a poly-aspartate motif (mScl hFc PD), were produced and purified using mammalian expression and standard chromatography methods. In vitro functionality and efficacy of the recombinant proteins were evaluated using three independent biophysical techniques and an in vitro bone nodule formation assay. Pharmacokinetic properties of the proteins were investigated in vivo following a single administration to young female wild type (WT) or SOST knock out (SOST-/-) mice. In a six week proof-of-concept in vivo study, young female WT or SOST-/- mice were treated with 10 mg/kg mScl hFc or mScl hFc PD (weekly), or 4.4 mg/kg mScl (daily). The effect of recombinant sclerostin on femoral cortical and trabecular bone parameters were assessed by micro computed tomography (μCT). Results: Recombinant mScl proteins bound to the extracellular domain of the Wnt co-receptor LRP6 with high affinity (nM range) and completely inhibited matrix mineralisation in vitro. Pharmacokinetic assessment following a single dose administered to WT or SOST-/- mice indicated the presence of hFc increased protein half-life from less than 5 min to at least 1.5 days. Treatment with mScl hFc PD over a six week period resulted in modest but significant reductions in trabecular volumetric bone mineral density (vBMD) and bone volume fraction (BV/TV), of 20% and 15%, respectively. Conclusion: Administration of recombinant mScl hFc PD partially corrected the high bone mass phenotype in SOST-/- mice, suggesting that bone-targeting of sclerostin engineered to improve half-life was able to negatively regulate bone formation in the SOST-/- mouse model of sclerosteosis. The translational potential of this article: These findings support the concept that exogenous sclerostin can reduce bone mass, however the modest efficacy suggests that sclerostin replacement may not be an optimal strategy to mitigate excessive bone formation in sclerosteosis, hence alternative approaches should be explored