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1.
Eur Thyroid J ; 11(1)2022 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-34981750

RESUMO

Objectives: Over 1.9 billion people worldwide are living in areas estimated to be iodine insufficient. Strategies for iodine supplementation include campaigns targeting vulnerable groups, such as women in pre-conception, pregnancy and lactation. Portuguese women of childbearing age and pregnant women were shown to be mildly-to-moderately iodine deficient. As a response, in 2013, the National Health Authority (NHA) issued a recommendation that all women considering pregnancy, pregnant or breastfeeding, take a daily supplement of 150-200 µg iodine. This study explored how the iodine supplementation recommendation has been fulfilled among pregnant and lactating women in Portugal, and whether the reported iodine supplements intake impacted on adverse obstetric and neonatal outcomes. Design and methods: Observational retrospective study on pregnant women who delivered or had a fetal loss in the Braga Hospital and had their pregnancies followed in Family Health Units. Results: The use of iodine supplements increased from 25% before the recommendation to 81% after the recommendation. This was mostly due to an increase in the use of supplements containing iodine only. Iodine supplementation was protective for the number of adverse obstetric outcomes (odds ratio (OR) = 0.791, P = 0.018) and for neonatal morbidities (OR = 0.528, P = 0.024) after controlling for relevant confounding variables. Conclusion: The recommendation seems to have succeeded in implementing iodine supplementation during pregnancy. National prospective studies are now needed to evaluate the impact of iodine supplementation on maternal thyroid homeostasis and offspring psychomotor development and on whether the time of the beginning of iodine supplementation (how early during preconception or pregnancy) is relevant to consider.

2.
Carbohydr Res ; 373: 97-102, 2013 May 24.
Artigo em Inglês | MEDLINE | ID: mdl-23603190

RESUMO

Ménière's disease (MD) is a progressive disease of the inner ear characterized by recurring attacks of disabling vertigo, hearing loss and tinnitus. Patients who do not respond to vestibular sedatives or steroids may require an intratympanic application of aminoglycoside antibiotics, which destroys the vestibular function of the affected ear in order to avoid the debilitating vertigo attacks. Although effective, this procedure causes hearing loss in almost one third of the patients due to the aminoglycosides cochlear toxicity. Here we describe the synthesis of two pseudodisaccharides structurally related to neamime aiming to mimic the aminoglycosides pharmacophore core by replacing their toxic amine by azide and hydroxyl groups. Products 1 and 2 selectively promoted 'in vivo' damage to vestibular tissues without causing hearing loss or cochlear toxicity. Therefore, these pseudodisaccharides stand as promising lead compounds for the development of a safer and more effective therapeutic procedure to manage the symptoms of MD severe dizziness.


Assuntos
Azidas/química , Azidas/farmacologia , Dissacarídeos/química , Dissacarídeos/farmacologia , Framicetina/química , Vertigem/tratamento farmacológico , Aminoglicosídeos/química , Animais , Azidas/síntese química , Técnicas de Química Sintética , Cóclea/citologia , Cóclea/efeitos dos fármacos , Dissacarídeos/síntese química , Avaliação Pré-Clínica de Medicamentos/métodos , Potenciais Evocados Auditivos do Tronco Encefálico/efeitos dos fármacos , Cobaias , Células Ciliadas Auditivas/efeitos dos fármacos , Humanos , Doença de Meniere/tratamento farmacológico , Microscopia Eletrônica de Varredura , Mimetismo Molecular , Estrutura Molecular
3.
J Phys Chem A ; 112(38): 8902-10, 2008 Sep 25.
Artigo em Inglês | MEDLINE | ID: mdl-18698751

RESUMO

In this work, we have used molecular dynamics, density functional theory, virtual screening, ADMET predictions, and molecular interaction field studies to design and propose eight novel potential inhibitors of CDK2. The eight molecules proposed showed interesting structural characteristics that are required for inhibiting the CDK2 activity and show potential as drug candidates for the treatment of cancer. The parameters related to the Rule of Five were calculated, and only one of the molecules violated more than one parameter. One of the proposals and one of the drug-like compounds selected by virtual screening indicated to be promising candidates for CDK2-based cancer therapy.


Assuntos
Quinase 2 Dependente de Ciclina/antagonistas & inibidores , Avaliação Pré-Clínica de Medicamentos/métodos , Modelos Moleculares , Neoplasias/tratamento farmacológico , Inibidores de Proteínas Quinases/farmacologia , Teoria Quântica , Animais , Biologia Computacional , Quinase 2 Dependente de Ciclina/química , Quinase 2 Dependente de Ciclina/metabolismo , Bases de Dados Factuais , Humanos , Conformação Proteica , Inibidores de Proteínas Quinases/química , Inibidores de Proteínas Quinases/metabolismo , Inibidores de Proteínas Quinases/toxicidade , Ratos , Termodinâmica
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