140 research outputs found

    Mutations in thyroid hormone transporter MCT8: genotype,function and phenotype

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    Mutations in thyroid hormone transporter MCT8: genotype,function and phenotype

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    Glucocorticoids

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    As one class of the most important steroid hormones, glucocorticoids have long been recognised and their therapeutic benefits have been widely used in clinical treatment, especially in anti-inflammation cases. Glucocorticoids regulate various processes in the body including the mobilization of energy stores, immune functions, gene expression, and maintenance of the homeostasis as well as the stress response, this is not surprising that the concept of "glucocorticoids" is mentioned in almost all medical text books that focus on specific organs or systems such as the cardiovascular system, the immune system, and the neuroendocrine system. The book of Glucocorticoids - New Recognition of Our Familiar Friend aims to introduce the latest findings relating to glucocorticoids, either freshly from the laboratory or from clinical case studies, and to open up a new angle of looking at the issue of balancing the therapeutic benefits and side effects brought up by glucocorticoids

    dna methylation as a predisposition factor in the pathogenesis of congenital hypothyroidism

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    Congenital hypothyroidism (CH) is the most frequent endocrinopathy in newborn. If not promptly treated lead to a severe impairment of psychomotor development. The etiophatogenesis of CH is still poorly understood; although several causative genes are identified, they can explain only a small portion of the pathological phenotypes. This scenario is further complicated if we focused on the incidence of CH in different context. In fact, epidemiological data indicate that children born prematurely have a 3-5 fold higher risk of CH. In addition premature infants born small for gestational age (SGA) have a risk of 12% higher to develop IC compared to prematures with appropriate development (AGA). The mechanisms that justify the increased risk of IC are still unknown. Some studies report that aberrant methylation patterns are associated with prematurity, intrauterine fetal development and the onset of some diseases. This project is focused on the study of DNA methylation, as predisposing factor to permanent thyroid dysfunction with neonatal onset. Using the Illumina Infinium-HumanMethylation27 technology we analyzed the global DNA methylation patterns (AVG\uf062) and selected the differentially methylated genes (DMGs) between 31 CH-cases born premature, AGA or SGA, and 28 term or preterm controls. To better understand the relationship between the DNA methylation and the premature birth, the intrauterine growth and the thyroid defect, the following groups were selected according to the gestational age at birth: 12 CH-with very preterm birth (CH-VPB37wks). The same subjects were then analyzed according to intrauterine growth (20 CH-SGA, 11 CH-AGA than 6 C-SGA and 20 C-AGA) or the degree of CH: 19 with overt CH (OH, TSH>10 \uf06dU/L) and 12 with mild CH (MH, TSH<10 \uf06dU/L) than 16 CPB and 12 CTB. The global methylation analysis showed that infants born prematurely and SGA have a significant hypomethylation than term-controls. These data were confirmed by the gene-specific methylation analysis, through which we selected a large group of differentially methylated genes (DMGs) in CH-cases than term controls. Interestingly, the 95% of the DMGs are hypomethylated and the 70% of them are represented by CpG sites located in DNA non-coding regions. The gene ontology analysis revealed that genes involved in fetal growth and thyroid hormone metabolism were included among DMGs. The analysis of nine maternal genomic DNA for polymorphisms at the MTHFR revealed the possible association with folate deficiency during pregnancy and the global hypomethylation status of affected newborns. This is the first work exploring the role of epigenetic influences in the predisposition to congenital hypothyroidism. Our results suggest that genomic instability caused by global hypomethylation of non-coding regions may be related to premature birth and fetal growth delay. Under these conditions, thyroid defects are more frequent than expected and could result from the increased expression of predisposing genes, rather than from the reduced expression of protective genes. The role of maternal conditions during pregnancy seems to be a key factor to determine a proper DNA methylation pattern on fetus. Based on the Developmental Origin of Health and Disease Theory, we can assume that adverse condition during pregnancy, such as folate deficiency, may produce a fetal epigenetic reprogramming and the adaptation of preterm neonate to the extrauterine life includes among other dysfunctions a thyroid functional impairment. If this data will be confirmed by further experiments, this could represent a new predisposing factor to take into account during pregnancy to prevent and improve the prenatal screening of CH

    Molecular Characterization of Extended-Spectrum beta-Lactamase-Producing Escherichia coli and Clones Causing Extraintestinal Infections in Humans. Animals as Reservoir of High-Risk E. coli Clones Pathogenic for Humans

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    Escherichia coli is the leading cause of urinary tract and bloodstream infections in humans and animals. The treatment of these infections has been seriously complicated by the appearance of multidrug-resistant isolates and especially by the rapid dissemination of extended-spectrum betalactamase- producing E. coli (ESBLEC). The present doctoral thesis includes six studies in which we evaluated the prevalence, the phenotypic and the genotypic characteristics of sequence type 131 (ST131) strains and other high-risk clones among E. coli strains isolated from patients with extraintestinal infections. We also study animals (pigs and dogs) as reservoirs for ST131 strains and other high-risk clones

    Health Goals for Perfluorinated Alkyl Substances (PFAS): A Review of Branched Isomers, the Role of Industrial Sources, and the Implications of Pfas in Biosolids on End-of-Life Disposal Methods

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    Per- and polyfluorinated alkyl substances, or PFAS, have been used for over half a century, but have become an emerging contaminant of significant concern due to their newly found widespread occurrence and recalcitrance in the environment, their tendency to bioaccumulate, and the health effects now associated with a very low level of exposure. Many gaps in knowledge remain about the fate of these chemicals in the environment and the extent of their impacts on biota. This thesis aims to fill some of the recognized gaps in knowledge: differences between linear and branched isomers of PFAS, predicting the presence of PFAS contamination in wells, and the implications of PFAS in municipal biosolids

    Hypoglycemia

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    Glucose is an essential metabolic substrate of all mammalian cells being the major carbohydrate presented to the cell for energy production and also many other anabolic requirements. Hypoglycemia is a disorder where the glucose serum concentration is usually low. The organism usually keeps the glucose serum concentration in a range of 70 to 110 mL/dL of blood. In hypoglycemia the glucose concentration normally remains lower than 50 mL/dL of blood. This book provides an abundance of information for all who need them in order to help many people worldwide

    Toxicological profile for polybrominated diphenyl ethers (PBDEs)

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    A Toxicological Profile for Polybrominated Diphenyl Ethers, Draft for Public Comment was released in September 2015. This edition supersedes any previously released draft or final profile

    Computational biology in human aging : an omics data integration approach

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    Throughout this thesis, human aging and its relation to health are studied in the context of two parallel though complementary lines of research: biomarkers and genetics. The search for informative biomarkers of aging focuses on easy accessible and quantifiable substances of the body that can be used to predict the early signs of deteriorating health, prior to the development of overt age-related disease. The challenge in this field is to translate the molecular changes captured by omics platforms to the age-associated deterioration observed at the whole body-level. In this thesis, new integrative methodology was developed that lead to the identification of gene expression networks that serve as biomarkers for aging and mortality. The second part of this thesis is aimed at identifying genetic determinants that predispose to a decelerated rate of aging and an extension of life span. Using whole genome sequencing data created in 218 nonagenarians of the Leiden Longevity Study we observed that a long life is not necessarily hampered by potentially premalignant somatic mutations in either TET2 or DNMT3A. In addition, genetic variation at chr13q34 attenuating the thyroid function, may be beneficial at middle age, but seems to contribute causally to increased mortality above 90 years.The Medical Delta Netherlands Consortium for Healthy AgeingUBL - phd migration 201
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