Copy number variations in “classical” obesity candidate genes are not frequently associated with severe early-onset obesity in children

Background: Obesity is genetically heterogeneous and highly heritable, although polymorphisms explain the phenotype in only a small proportion of obese children. We investigated the presence of copy number variations (CNVs) in “classical” genes known to be associated with (monogenic) early-onset obesity in children. Methods: In 194 obese Caucasian children selected for early-onset and severe obesity from our obesity cohort we screened for deletions and/or duplications by multiplex ligation-dependent probe amplification reaction (MLPA). As we found one MLPA probe to interfere with a polymorphism in SIM1 we investigated its association with obesity and other phenotypic traits in our extended cohort of 2305 children. Results: In the selected subset of most severely obese children, we did not find CNV with MLPA in POMC, LEP, LEPR, MC4R, MC3R or MC2R genes. However, one SIM1 probe located at exon 9 gave signals suggestive for SIM1 insufficiency in 52 patients. Polymerase chain reaction (PCR) analysis identified this as a false positive result due to interference with single nucleotide polymorphism (SNP) rs3734354/rs3734355. We, therefore, investigated for associations of this polymorphism with obesity and metabolic traits in our extended cohort. We found rs3734354/rs3734355 to be associated with body mass index-standard deviation score (BMI-SDS) (p = 0.003), but not with parameters of insulin metabolism, blood pressure or food intake. Conclusions: In our modest sample of severely obese children, we were unable to find CNVs in well-established monogenic obesity genes. Nevertheless, we found an association of rs3734354 in SIM1 with obesity of early-onset type in children, although not with obesity-related traits

Concomitância da tireoidite de Hashimoto e o carcinoma diferenciado da tireóide

OBJETIVO: Avaliar a associação da tireoidite auto-imune e o carcinoma diferenciado da tireóide na Santa Casa de Misericórdia de Goiânia-Goiás. MÉTODO: De 1395 tireoidectomias realizadas de 1994 a 2003, foram selecionadas 120 carcinomas diferenciados (27 foliculares e 93 papilíferos). Foram avaliadas as variáveis clínicas (idade e sexo) com apresentação de freqüências e de sumários de medidas-resumo na descrição estatística. Para aferir a associação de tireoidite auto-imune e carcinoma diferenciado da tireóide em função dos achados histopatológicos, utilizou-se tabelas de contingência e análise pelo teste não paramétrico do quiquadrado de Pearson. Em todos os testes estatísticos foi adotado um nível de significância de 5% (p<0,05). RESULTADOS: 11,1% dos carcinomas foliculares e 18,3% dos carcinomas papilíferos estão associados à tireoidite auto-imune. Existe uma relação de freqüências quatro vezes maior da tireoidite auto-imune com o carcinoma diferenciado da tireóide em comparação com outras doenças tireoideanas (16,7% X 3,6%). CONCLUSÕES: Tais resultados permitem inferir que a associação entre a tireoidite auto-imune e o carcinoma diferenciado da tireóide é mais que casual, exigindo uma observação clínico-laboratorial cuidadosa nos portadores da doença auto-imune

Probing intermetallic coupling in dinuclear N-heterocyclic carbene ruthenium(II) complexes

A series of bimetallic N-heterocyclic carbene (NHC) ruthenium(II) complexes were synthesized, which comprise two [RuCl₂(cymene)(NHC)] units that are interlinked via the NHC nitrogens by alkyl chains of different length. Electrochemical characterization revealed two mutually dependent oxidation processes for the complex with a methylene linker, indicating moderate intramolecular electronic coupling of the two metal centers (class II system). The degree of coupling decreases rapidly upon increasing the number of CH₂ units in the linker and provides essentially decoupled class I species when propylene or butylene linkers are used. Electrochemical analyses combined with structural investigations suggest a through-bond electronic coupling. Replacement of the alkyl linker with a p-phenylene group afforded cyclometalated complexes, which were considerably less stable. The electronic coupling in the methylene-linked complex and the relatively robust NHC–ruthenium bond may provide access to species that are switchable on the molecular scale