Protocol for: Sheffield Obesity Trial (SHOT): A randomised controlled trial of exercise therapy and mental health outcomes in obese adolescents [ISRCNT83888112]

Background  

While obesity is known to have many physiological consequences, the psychopathology of this condition has not featured prominently in the literature. Cross-sectional studies have indicated that obese children have increased odds of experiencing poor quality of life and mental health. However, very limited trial evidence has examined the efficacy of exercise therapy for enhancing mental health outcomes in obese children, and the Sheffield Obesity Trial (SHOT) will provide evidence of the efficacy of supervised exercise therapy in obese young people aged 11–16 years versus usual care and an attention-control intervention.     

Local metabolism in lung airways increases the uncertainty of pyrene as a biomarker of polycyclic aromatic hydrocarbon exposure

While inhaled polycyclic aromatic hydrocarbons have long been suspected to induce lung cancer in humans, their dosimetry has not been fully elucidated. A key question is whether the critical exposure occurs during absorption in the lungs, or if toxicants in the systemic circulation contribute significantly to lung cancer risk. In particular, data are needed to determine how the physical properties of inhalants affect local dosimetry in the respiratory tract. Pyrene, a tobacco smoke component, was selected for study because it has physical properties between those of highly lipophilic benzo[a]pyrene and water- soluble nitrosamines. Aliquots of 5 ng of pyrene dissolved in a phospholipid/ saline suspension were instilled as a single-spray bolus in the posterior trachea of the dog just anterior to the carina. For 3 h after instillation, blood was repeatedly sampled from the azygous vein, which drains the mucosa around the point of instillation, and from both sides of the systemic circulation. At 3 h post-instillation, tissue samples were taken. Autoradiography was used to determine the depth distribution of pyrene in the tracheal mucosa. The concentration of pyrene-equivalent radioactivity in the azygous vein peaked 9 min after the instillation. At approximately 30 min after instillation, a rapid early clearance phase shifted into a distinctly slower second clearance phase. Rates of rapid clearance were, however, sufficiently slow to indicate diffusion-limited absorption of pyrene in the trachea. This finding was corroborated by high concentrations of pyrene in the epithelium as determined by autoradiography. High epithelial concentration of pyrene combined with a slow penetration into the circulating blood allowed substantial first-pass metabolic conversion of pyrene in the tracheal mucosa. A total of 13% of the instilled pyrene was retained in the tracheal mucosa 3.2 h after instillation; of this, 29% was parent compound, 52% was organic-extractable metabolites, 14% was water-soluble metabolites and 6% (approximately 1% of the instilled amount) was covalently bound to tracheal tissues. Results support the inference that lipophilic protoxicants, because of slow, diffusion-limited absorption, are more likely than water-soluble protoxicants to be bioactivated in the lining epithelium and, in turn, induce first-pass toxicity at the site of entry. In addition, limitations were identified in the use of systemically distributed biomarkers of PAHs, such as urinary hydroxypyrene levels, as indicators of the biologically effective dose in airway target cells.      

Peritoneal interleukin-10 increases with decrease in activated CD4+ T lymphocytes in women with endometriosis

This study was performed to determine whether peritoneal T cells are suppressed in the CD4+ or CD8+ T cell subpopulation and whether they are Th1 or Th2 predominant in women with endometriosis. Immune cells in the peritoneal fluid (PF) were obtained from women undergoing laparoscopy for endometriosis or tubal ligation. Three-colour flow cytometry was utilized for immunophenotyping of peritoneal fluid mononuclear cells (PFMC). Concentrations of interleukin (IL)-4, IL-5 and interferon-gamma (IFN-gamma) produced by PFMC with and without mitogen stimulation and concentrations of IL-10 and IL-12 were measured in PF. The peritoneal T lymphocytes were predominantly of the Th1 type that produced much more IFN-gamma but less IL-4 or IL-5 in women with or without endometriosis. The decrease in peritoneal lymphocytes was significant in the HLA-DR+ CD4+ CD3+ subpopulation and the concentrations of peritoneal IL-10 and IL-12 were significantly elevated in women with early stage endometriosis. There was impaired IL- 5 production by PFMC after phytohaemagglutinin stimulation in women with advanced stage endometriosis. We concluded that the activated peritoneal CD4+ Th1 cells from the women with endometriosis were decreased in number. The suppression of these T cells may be due to the elevation of IL-10 and IL-12 in the peritoneal fluid.      

Paired human chorionic gonadotrophin determinations for the prediction of pregnancy outcome in assisted reproduction

The aim of this study was to determine the prognostic value of single and paired measurements of serum concentrations of human chorionic gonadotrophin (HCG) for successful pregnancy following in-vitro fertilization (IVF) and tubal embryo transfer (TET). We analysed serum HCG concentrations 15 and 22 days after IVF or TET in 198 conception cycles. Cut-off values of serum HCG were determined by a receiver operating characteristic (ROC) curve. On the basis of single HCG samples on day 15 (HCG15) after transfer, using a cut-off value of HCG15 = 150 mIU/ml, the sensitivity was 71% and the specificity was 77%. The positive predictive value (HCG15 > or = 150 mIU/ml indicating a normal pregnancy) was 89%, while the negative predictive rate (HCG15 < 150 mIU/ml indicating an abnormal pregnancy) was 51%. Patients with HCG15 < 150 mIU/ml but HCG22/HCG15 ratio > or = 15, still had a 90% chance of normal pregnancy. However, in patients with HCG15 < 150 mIU/ml and an HCG22/HCG15 ratio < 15, there was an 84% chance of an abnormal pregnancy. We conclude that a single HCG15 determination combined with the ratio of HCG22 to HCG15 has a higher diagnostic accuracy for prediction of pregnancy outcome than either analysis alone.      

Total antioxidant status and nitric oxide do not increase in peritoneal fluids from women with endometriosis

To explore the role of nitric oxide (NO) and oxidative stress in the pathogenesis of adhesion formation and in endometriosis-associated infertility, we examined the peritoneal total antioxidant status (TAS) and the concentrations of products of NO metabolism in women with endometriosis (early stage, n = 12; advanced stage, n = 12) and in fertile women without endometriosis (n = 10). Peritoneal CA 125 and oestrogen and progesterone concentrations were also measured to examine their contributions to TAS and the production of NO. We failed to demonstrate any significant difference in TAS and in the products of NO metabolism in peritoneal fluids among women with early and advanced stages of endometriosis compared with fertile women without endometriosis during the early follicular phase. TAS and the concentration of the products of NO metabolism were not related to concentrations of CA 125, oestrogen or progesterone. The concentration of CA 125 in serum, but not in peritoneal fluid, was positively correlated with the severity of endometriosis. The volume of peritoneal fluid and the progesterone concentration were significantly increased in the group with advanced endometriosis. TAS and the concentration of the products of NO metabolism did not increase in peritoneal fluids from women with endometriosis during the early follicular phase. Their role in the pathophysiology of endometriosis needs to be explored further.      

Synthesis and properties of high-molecular-weight polyesters based on 1,4:3,6-dianhydrohexitols and terephthalic acid

The synthesis of high-molecular-weight polyesters based on 1,4:3,6-dianhydro-D -sorbitol (DAS), 1,4:3,6-dianhydro-D -mannitol (DAM) and 1,4:3,6-dianhydro-L -iditol (DAI) is reported. The polymers were obtained by polycondensation in solution of the dianhydrohexitols with terephthaloyl dichloride and 2,5-diethoxyterephthaloyl dichloride. The side groups of the latter monomer lead to a marked improvement of the solubility of the resulting polyesters which can be characterized by NMR techniques and osmometry. It is shown that all polyesters exhibit an excellent stability against thermal decomposition. Materials deriving from the polycondensation with terephthalic acid have glass transitions above 200°C if the molecular weight is high enough. The wide-angle X-ray analysis shows that polyesters deriving from terephthalic acid and DAM as well as DAI are semicrystalline. All results demonstrate that these polyesters partly deriving from renewable carbon sources present promising high T_g materials with excellent thermal stability.