Influence of Neonatal Hypothyroidism on Hepatic Gene Expression and Lipid Metabolism in Adulthood

Thyroid hormones are required for normal growth and development in mammals. Congenital-neonatal hypothyroidism (CH) has a profound impact on physiology, but its specific influence in liver is less understood. Here, we studied how CH influences the liver gene expression program in adulthood. Pregnant rats were given the antithyroid drug methimazole (MMI) from GD12 until PND30 to induce CH in male offspring. Growth defects due to CH were evident as reductions in body weight and tail length from the second week of life. Once the MMI treatment was discontinued, the feed efficiency increased in CH, and this was accompanied by significant catch-up growth. On PND80, significant reductions in body mass, tail length, and circulating IGF-I levels remained in CH rats. Conversely, the mRNA levels of known GH target genes were significantly upregulated. The serum levels of thyroid hormones, cholesterol, and triglycerides showed no significant differences. In contrast, CH rats showed significant changes in the expression of hepatic genes involved in lipid metabolism, including an increased transcription of PPARα and a reduced expression of genes involved in fatty acid and cholesterol uptake, cellular sterol efflux, triglyceride assembly, bile acid synthesis, and lipogenesis. These changes were associated with a decrease of intrahepatic lipids. Finally, CH rats responded to the onset of hypothyroidism in adulthood with a reduction of serum fatty acids and hepatic cholesteryl esters and to T3 replacement with an enhanced activation of malic enzyme. In summary, we provide in vivo evidence that neonatal hypothyroidism influences the hepatic transcriptional program and tissue sensitivity to hormone treatment in adulthood. This highlights the critical role that a euthyroid state during development plays on normal liver physiology in adulthood

Specific allergen immunotherapy for the treatment of allergic asthma: a review of current evidence.

Asthma is frequently associated with atopy, characterized by the production of specific immunoglobulin E in response to environmental allergens. Currently, two types of allergen immunotherapy (AIT) are used in clinical practice: subcutaneous and sublingual immunotherapy, both accepted as key components of the therapeutic repertoire for allergic rhinitis and conjunctivitis. However, their role in asthma remains controversial. The present document is aimed at providing the clinicians with a review of the evidence on the use of AIT in asthma, focusing on the most relevant aspects of its mechanism of action, its efficacy, and existing data on safety, tolerability, and cost-effectivity, both in pediatric and adult populations. A systematic search of MEDLINE, Cochrane, and Clinical Trials databases from 2000 to April of 2016 was carried out by a panel of experts from the Spanish Allergy and Clinical Immunology Scientific Society. Relevant studies prior to the year 2000 included in ulterior systematic reviews were also considered. More than 4000 articles were identified during the search and 241 were selected to retrieve available evidence on AIT, which was graded according to the Oxford classification. All the group members reviewed the resulting text until the final version reached the consensual agreement. A summary of recommendations on the more relevant topics are proposed. The role of AIT as a valuable therapeutic strategy for prevention of exacerbation and progressive decline in lung function is highlighted. Future research should include specific tools for asthma evaluation when assessing AIT effectiveness in asthmatic patients

ESICM LIVES 2016: part two : Milan, Italy. 1-5 October 2016.

Meeting abstrac