Rearrangements of unsaturated steroid alcohols

The action of toluene-p-sulphonyl chloride in pyridine on cholest-4-en-3ß-ol and on 5a-cholest-l-en-3ß-ol has been investigated; in neither case was a tosyl ester isolated. The former reaction produced 3a,5-cyclo-5a-cholest-6-ene, cholesta-3,5-diene and N-(cholest-4-en-3a-yl)-pyridinium tosylate. In the latter case, the products isolated were la,5-cyclo-5a-cholest-2-ene and N-(cholest-l-en-3a-yl)-pyridinum tosylate.la,5-Cyclo-5a-cholest-2-ene has been characterised by both its spectral properties and chemical reactions. The ultra violet and infra red spectra are consistent with the assigned alkyl-cyclopropane structure; indeed the proton magnetic resonance spectrum also supports the structure, but assignment of peaks was uncertain. The ambiguity was resolved by consideration of the p.m.r. spectrum of 17ß- methoxy-la,5-cyclo-5a-androst-2-ene, synthesised from 17ß-methoxy-5a-androst-l-en-3ß-ol by the same method. This reaction also produced l7ß- methoxy- 5a- androsta-1,3-diene in addition to the cyclosteroid.The major reactions of la,5-cyclo-5a-cholest-2-ene are summarised below. Catalytic reduction using palladium on charcoal catalyst afforded 5a-cholestane, but use of the soluble catalyst, tris(triphenylphosphine)rhodium chloride, gave la,5-cyclo-5a-cholestane. Oxidative fission of the olefinic bond followed by reductive cleavage of the cyclopropane ring afforded the known diacid, 2,3-seco-cholestan-2,3-dioic. Reaction of peracid with the hydrocarbon gave a mono-oxide, cleaved with lithium aluminium hydride to give 1a,5-cyclo-5a-cholestan-2a-ol. The cyclopropyl-ketone obtained from the oxidation of this alcohol was reduced catalytically to dive 5a-cholestan-2-one. la,5-Cyclo-5a-cholestane was obtained from this ketone by Wolff- Kishner reduction.la,5-Cyclo-5a-cholestane has also been synthesised by a separate reaction sequence, the cyclopropane ring being introduced by dehydration of a suitably substituted 5ß-hydroxy compound, and proved to be identical with the material obtained in the above reactions.A possible mechanism for the formation la,5-cyclo-5a-cholest-2-ene from 5a-cholest-l-en-3ß-ol has been proposed, involving transannular migration of the 5a-hydrogen atom. Results from tosylation experiments on 5a-deutero and 5a-fluoro-cholest-l-en3ß-ol have substantiated this mechanism.Attempted tosylation of 19-nor-androst-4-en-3ß-ol and 19-nor5a-androst-l-en-3ß-ol gave estra-3,5(10)-diene and estra-l,3-diene respectively; no cyclosteroids were isolated.A synthesis of estradiol from 17ß-acetoxy-androst-1,4,6-trien3-one has been carried out. Aromatisation of this trienone with sulphuric acid under anhydrous conditions gave 17ß-acetoxy-l-methyl-estra-1,3,5(10) -trien-3-one. Removal of the l-methyl group was effected in two stages: Oxidation with cerium (IV) gave the l-formyl derivative, which was decarbonylated with tris-(triphenylphosphine) rhodium chloride

Jubilee mugs:the monarchy and the Sex Pistols

With rare exceptions sociologists have traditionally had little to say about the British monarchy. In the exceptional cases of the Durkheimian functionalism of Shills and Young (1953), the left humanism of Birnbaum (1955), or the archaic state/backward nation thesis of Nairn (1988), the British nation has been conceived as a homogenous mass. The brief episode of the Sex Pistols' Jubilee year song 'God Save the Queen' exposed some of the divisions within the national 'mass', forcing a re-ordering of the balance between detachment and belonging to the Royal idea. I argue that the song acted as a kind of 'breaching experiment'. Its wilful provocation of Royalist sentiment revealed the level of sanction available to the media-industrial complex to enforce compliance to British self-images of loyal and devoted national communicants

Serum 25-Hydroxyvitamin D and Intact Parathyroid Hormone Influence Muscle Outcomes in Children and Adolescents

Increases in 25-hydroxyvitamin D concentrations are shown to improve strength in adults; however, data in pediatric populations are scant and equivocal. In this ancillary study of a larger-scale, multi-sited, double-blind, randomized, placebo-controlled vitamin D intervention in US children and adolescents, we examined the associations between changes in vitamin D metabolites and changes in muscle mass, strength, and composition after 12 weeks of vitamin D3 supplementation. Healthy male and female, black and white children and adolescents between the ages of 9 and 13 years from two US states (Georgia 34°N and Indiana 40°N) were enrolled in the study and randomly assigned to receive an oral vitamin D3 dose of 0, 400, 1000, 2000, or 4000 IU/d for 12 weeks between the winter months of 2009 to 2011 (N = 324). Analyses of covariance, partial correlations, and regression analyses of baseline and 12-week changes (post-baseline) in vitamin D metabolites (serum 25(OH)D, 1,25(OH)2 D, intact parathyroid hormone [iPTH]), and outcomes of muscle mass, strength, and composition (total body fat-free soft tissue [FFST], handgrip strength, forearm and calf muscle cross-sectional area [MCSA], muscle density, and intermuscular adipose tissue [IMAT]) were assessed. Serum 25(OH)D and 1,25(OH)2 D, but not iPTH, increased over time, as did fat mass, FFST, forearm and calf MCSA, forearm IMAT, and handgrip strength (p < 0.05). Vitamin D metabolites were not associated with muscle strength at baseline nor after the 12-week intervention. Changes in serum 25(OH)D correlated with decreases in forearm IMAT, whereas changes in serum iPTH predicted increases in forearm and calf MCSA and IMAT (p < 0.05). Overall, increases in 25(OH)D did not influence muscle mass or strength in vitamin D-sufficient children and adolescents; however, the role of iPTH on muscle composition in this population is unknown and warrants further investigation

Racial Differences in Cortical Bone Mass, Size and Estimated Strength at the Tibial Diaphysis in Early Pubertal Children

poster abstractOsteoporotic fracture rates differ according to race, with blacks having up to half the rate of whites. The reduced fracture rate in blacks has been suggested to be due to their superior bone mass; however, mass is not the sole determinant of bone strength. Bone strength, and consequent fracture risk, is also influenced by how bone material is distributed or structured. It is likely bone structure also contributes to the lower incidence of fractures in blacks and that racial differences in bone structure have roots in childhood. The aim of this study was to assess the influence of race on pQCT-derived cortical bone mass, size and estimated strength at the tibial diaphysis in early pubertal children. 160 children were recruited, with equal subjects according to race (black, n=80; white, n=80) and sex (female, n=80; male, n=80). Subjects were at sexual maturation stages 2 or 3. Tomographic slices of the tibial diaphysis at 66% proximal from the medial malleolus were acquired using pQCT. Slices were assessed for cortical volumetric BMD (Ct.vBMD), cortical BMC (Ct.BMC), total (Tt.Ar) and cortical (Ct.Ar) area, density weighted maximum (IMAX) and minimum (IMIN) second moments of area, density-weighted polar strength-strain index (SSIP), and muscle cross-sectional area (mCSA). Group differences were assessed by two-way analysis of covariance, with race (black vs. white) and sex (female vs. male) as independent variables. Covariates included predicted years from peak height velocity (maturity offset), tibial length and mCSA. There were no interactions between race and sex (all P=0.50-0.98) or main effect for sex (all P=0.08-0.45). Blacks had 15.7% more Ct.BMC, and 10.8-11.8% larger Tt.Ar and Ct.Ar than whites (all P<0.001). The greater enhancement of Ct.BMC relative to Ct.Ar resulted in blacks having 3.6% greater Ct.vBMD than whites (P<0.001). The combination of increased cortical bone mass, size and density in blacks contributed to enhanced estimated bone strength, with IMAX, IMIN and SSIP being 20.0%, 34.5% and 25.2% greater in blacks than whites, respectively (all P<0.001). These data indicate that early pubertal black children have enhanced bone mass, size and estimated bone strength at the tibial diaphysis versus whites, independent of tibial length and mCSA. They suggest bone structural differences may contribute to observed racial differences in fracture rates and that structural divergence between races develops during childhood

Exploring engaged spaces in community-university partnership

The Community University Partnership Programme (CUPP) has been operating at the University of Brighton for the past 10 years. This article explores the different types of space we think need to exist to support a variety of partnership and engaged work. We therefore explore our understandings of shared or ‘engaged' spaces as a physical, virtual and relational phenomenon in this context

(Re)discovering the Gaulcross Hoard

Acknowledgements We would like to thank Charles and Helen Gray for permitting access to the land and for support in the excavation of the hoard. Thanks also to Bruce Mann and the Aberdeenshire Council Archaeology Service for advice and supporting the radiocarbon dating. Fraser Hunter and Tanja Romankiewicz assisted during a very cold excavation. Fraser and Alice Blackwell kindly read and commented on drafts of this paper. The fieldwork was funded through a donation to the University of Aberdeen's Development Trust and undertaken as part of the Northern Picts project, in association with the Tarbat Discovery Centre.Peer reviewedPostprin

Desmopressin for prevention of bleeding for thrombocytopenic, critically ill patients undergoing invasive procedures: A randomised, double‐blind, placebo‐controlled feasibility trial

Thrombocytopenic patients have an increased risk of bleeding when undergoing invasive procedures. In a multicentre, phase II, blinded, randomised, controlled feasibility trial, critically ill patients with platelet count 100 × 109/L or less were randomised 1:1 to intravenous desmopressin (0.3 µg/kg) or placebo before an invasive procedure. Forty‐three participants (18.8% of those eligible) were recruited, with 41 eligible for analysis. Post‐procedure bleeding occurred in one of 22 (4.5%) in the placebo arm and zero of 19 in the desmopressin arm. Despite liberal inclusion criteria, there were significant feasibility challenges recruiting patients in the critical care setting prior to invasive procedures

Insulin Resistance and the IGF-I-Cortical Bone Relationship in Children Ages 9-13 Years

IGF-I is a pivotal hormone in pediatric musculoskeletal development. Although recent data suggest that the role of IGF-I in total body lean mass and total body bone mass accrual may be compromised in children with insulin resistance, cortical bone geometric outcomes have not been studied in this context. Therefore, we explored the influence of insulin resistance on the relationship between IGF-I and cortical bone in children. A secondary aim was to examine the influence of insulin resistance on the lean mass-dependent relationship between IGF-I and cortical bone. Children were otherwise healthy, early adolescent black and white boys and girls (ages 9 to 13 years) and were classified as having high (n = 147) or normal (n = 168) insulin resistance based on the homeostasis model assessment of insulin resistance (HOMA-IR). Cortical bone at the tibia diaphysis (66% site) and total body fat-free soft tissue mass (FFST) were measured by peripheral quantitative computed tomography (pQCT) and dual-energy X-ray absorptiometry (DXA), respectively. IGF-I, insulin, and glucose were measured in fasting sera and HOMA-IR was calculated. Children with high HOMA-IR had greater unadjusted IGF-I (p < 0.001). HOMA-IR was a negative predictor of cortical bone mineral content, cortical bone area (Ct.Ar), and polar strength strain index (pSSI; all p ≤ 0.01) after adjusting for race, sex, age, maturation, fat mass, and FFST. IGF-I was a positive predictor of most musculoskeletal endpoints (all p < 0.05) after adjusting for race, sex, age, and maturation. However, these relationships were moderated by HOMA-IR (pInteraction < 0.05). FFST positively correlated with most cortical bone outcomes (all p < 0.05). Path analyses demonstrated a positive relationship between IGF-I and Ct.Ar via FFST in the total cohort (βIndirect Effect = 0.321, p < 0.001). However, this relationship was moderated in the children with high (βIndirect Effect = 0.200, p < 0.001) versus normal (βIndirect Effect = 0.408, p < 0.001) HOMA-IR. These data implicate insulin resistance as a potential suppressor of IGF-I-dependent cortical bone development, though prospective studies are needed